In most episodes, the word "sex" is spoken an average 25 times.

Molly Ringwald sings the show's theme song "Let's Do It, Let's Fall In Love" written by Cole Porter.

During the beginning of filming, Shailene Woodley had to wear a back brace to correct her scoliosis.

The series is made by the same producers as 7th Heaven. When Amy is soon to be in labor she asks for a Dairy Shack burger which is the same fast food restaurant in 7th Heaven that Matt Camden was once a delivery boy for.

Daren Kagastoff (Ricky) is four years older than Shailene Woodley (Amy)

Cierra Ramirez and Marlene Forte also played grandmother and granddaughter in The Fosters.

Stills of Renee Olstead's character Madison Cooperstein in Secret Life prominently appear in her film Unfriended as her character's past facebook photos, visible on her timeline and only stills of her blonde hairdo of the show, utilized by the film's writer Nelson Greaves so as to suggest her character Jess Felton in Unfriended was a natural blonde.

Shailene Woodley (Amy Jurgens) And John Schneider (Marshall Bowman) played father and daughter in the 2005 movie, Felicity: An American Girl Adventure based on the American girl doll.

Jennifer Coolidge (Betty) was the stepmother in A Cinderella story and Megan Park played the step sister in A Cinderella story: once upon a song.

Daren Kagasoff was handpicked By Brenda Hampton the creator of the show.

Madison Cooperstein's Renee Olstead would go on to star in the acclaimed teenage slasher horror film Unfriended which also features Courtney Halverson as main teen victim character Valerie Rommel, Halverson makes a single episode appearence in Secret Life in a very small role in a scene with Olstead and the two as their respective characters of Jess Felton and Val Rommel in Unfriended are against each other in argument, paralleling their shared scene in Secret Life.

In the 12th episode of the third season, a reference to Sixteen Candles (1984) is made by Molly Ringwald, a lead role in the film and Amy's mother in Secret Life of an American Teenager. In this episode she says that when she turned 16, everybody forgot her birthday which is a main plot that happens to her character in the film.

Molly Ringwald was actually pregnant in real life with her twins, Roman Stylianos Gianopoulos and Adele Georgiana Gianopoulos, when she appeared pregnant as her on-screen counterpart, Anne Juergens.

In the episode where Anne and George forget Amy's 16th birthday while she is in New York, Anne, played by Molly Ringwald, makes a comment that on her own 16th birthday her entire family forgot, ruining her life. Molly Ringwald previously starred in the movie Sixteen Candles, where she plays the main character, Samantha, and the plot is based upon Samantha's family forgetting her 16th birthday.

In season 1 episode 4 John Schneider (Dr Bowman) makes a reference to his former roll and co. stars on Dukes of Hazzard by saying his daughter could become a Rent-A-Cop which is something that Boss Hogg (Sorrell Booke) frequently threatens Roscoe P. Coltrane (James Best) with throughout the show