The second season of Joey aired from September 22, 2005 to July 5, 2006.
- Matt LeBlanc as Joey Tribbiani, who moves to Los Angeles from New York, to proceed with his acting career. He is constantly talking about food or eating sandwiches.
- Paulo Costanzo as Joey's nephew Michael Tribbiani who idolizes his Uncle Joey's ability to date many women, and who himself is sheltered and nervous around girls. He is self-conscious that he has been so sheltered and that his mother Gina breast fed him until he was seven. He is a huge Star Trek: The Next Generation and Star Wars fan. He is extremely intelligent, an aerospace engineer, attends Caltech and specializes in applied thermodynamics, works with his rival Seth frequently on engineering projects, and is an obvious direct opposite from his more street-wise mother and uncle. Turns to Joey as a big brother and substitute father figure, even after his biological father Jimmy has re-entered mother Gina's love life Joey soon spits out to Jimmy that he is Michael's father. He plays a smaller role in the second season.
- Drea de Matteo as Joey's attractive older sister Gina Tribbiani, who is temperamental and promiscuous. Not particularly bright but very street-wise, Gina is a caring but over-protective and domineering mother. For years she convinced her genius son Michael that he was born when she was 22, instead of 15 and always says he is the one thing she has done really well. She and Joey are friends in addition to being siblings, both having the gift of being extremely appealing to the opposite sex, with numerous lovers. Initially working as a hair dresser, by season two she works as a secretary for Joey's agent Bobbie, having impressed Bobbie with her brash manner. In season two she starts dating Michael's father Jimmy once again and marries him.
- Andrea Anders as Alexis "Alex" Garrett, the next door neighbour, landlord and friend. She is an educated, but slightly ditsy blonde lawyer who graduated from Pepperdine University. Initially intimidated, but also intrigued by Joey's tough street-wise older sister Gina, the two women eventually become friends, and she becomes more bold in the way she dresses and acts, thanks to Gina's influence. She is puzzled but impressed by Joey's gift at being able to know when she is wearing thong panties, and spends most of her time hanging out at Joey and Michael's apartment. She and Joey bond and become close friends, and she confides in him her problems with her marriage. Her husband is a professional orchestra musician and is away from home most of the time. By the end of season one, she and Joey become romantically involved during her separation from her husband. In season two she becomes romantically interested in Joey and has a crush on him for a long while and Gina tries to help her to get over him, once she starts dating Joey's friend Dean, Joey soon realizes that he is also in love with Alex.
- Jennifer Coolidge as Joey's oversexed agent Roberta "Bobbie" Morganstern, and reportedly the 12th most powerful woman in Hollywood. She has an enormous crush on Joey's nephew Michael. She often entertains herself by making her office assistant do funny tricks, or shocking herself with a stun-gun. She is brash, forward, aggressive, highly entertaining and slightly ditsy, laughing at everything and at anyone's expense, including her client Joey's. She was once sued by Phil Collins.
- Miguel A. Núñez Jr. joined the cast at the start of season two as the character Zach Miller. He soon became one of Joey's best friends. Zach has an interesting career, going from playing extras on TV, to directing amateur plays. Zach does not appear to have a home; he was seen at one time living in Joey's trailer, while he was working on a major blockbuster movie. In one episode, Zach and Joey, both drunk, married in Tijuana, possibly a parody of Ross and Rachel marrying each other in the season five finale of Friends. Possibly as a tribute to Joey and Chandler, Joey and Zach argued like a married couple, Zach playing the part of the wife. Zach's final appearance was in "Joey And The Big Move". Núñez was absent from the last five episodes, including the finale of the series, due to having found another job. Zach's absence within the show was not mentioned, nor was the character at all.
|1||25||"Joey and the Big Break, Part 1"||Scott Silveri||Kevin S. Bright||September 22, 2005|
|Things become awkward between Joey and Alex after having sex. Due to Joey's popularity on Deep Powder, Bobbie makes some outrageous demands leading to him being fired. Gina starts working for Bobbie. A young aspiring actress moves in the complex and thinks Michael is Joey.|
|2||26||"Joey and Big Break, Part 2"||Robert Carlock||Kevin S. Bright||September 22, 2005|
|Hearing voices in his head causes Joey to blow a couple of auditions. Gina gets to tell everyone bad news for Bobbie, Michael wants Joey to go on a double date with him, and Alex wants Joey to take her on a romantic date so she feels better about sleeping with him.|
|3||27||"Joey and the Spanking"||Michael Borkow||Kevin S. Bright||September 29, 2005|
|4||28||"Joey and the Stuntman"||John Quaintance||Kevin S. Bright||October 6, 2005|
|5||29||"Joey and the House"||Brett Baer & Dave Finkel||Ben Weiss||October 13, 2005|
|6||30||"Joey and the ESL"||Vanessa McCarthy||Peter Bonerz||October 20, 2005|
|7||31||"Joey and the Poker"||Matt Hubbard||Kevin S. Bright||November 3, 2005|
|8||32||"Joey and the Sex Tape"||Linda Videtti Figueiredo||Kevin S. Bright||November 10, 2005|
|9||33||"Joey and the Musical"||Vanessa McCarthy||Gary Halvorson||November 17, 2005|
|10||34||"Joey and the Bachelor Thanksgiving"||John Quaintance||Kevin S. Bright||November 24, 2005|
|11||35||"Joey and the High School Friend"||Michael Borkow||Sheldon Epps||December 8, 2005|
|12||36||"Joey and the Tijuana Trip"||Robert Carlock||Gary Halvorson||December 15, 2005|
|13||37||"Joey and the Christmas Party"||Matt Hubbard & Linda Videtti Figueiredo||Gary Halvorson||December 15, 2005|
|14||38||"Joey and the Snowball Fight"||Tracy Reilly & Matt Hubbard||Kevin S. Bright||March 7, 2006|
|15||39||"Joey and the Dad"||Robert Carlock & John Quaintance||Kevin S. Bright||April 18, 2006 (in Latin America)|
|16||40||"Joey and the Party For Alex"||Vanessa McCarthy||Gil Cates Jr.||May 9, 2006 (in Latin America)|
|17||41||"Joey and the Big Move"||Jean Yu||Gary Halvorson||May 16, 2006 (in Latin America)|
|18||42||"Joey and the Beard"||Dan Holden & Linda Videtti Figueiredo||Peter Bonerz||May 23, 2006 (in Latin America)|
|19||43||"Joey and the Critic"||Michael Borkow||Ben Weiss||June 6, 2006 (in Ireland)|
|20||44||"Joey and the Actor's Studio"||John Quaintance||Kevin S. Bright||June 28, 2006 (in Ireland)|
|21||45||"Joey and the Holding Hands"||Vanessa McCarthy & Robert Carlock||Peter Bonerz||May 30, 2006 (in Latin America)|
|22||46||"Joey and the Wedding"||Alison Flierl & John Quaintance||Kevin S. Bright||August 23, 2006 (in Latin America)|