During the filming, Gene Roddenberry was in a panic because he needed at least two female identical twins and couldn't find any. Then one night while driving home he saw Alyce Andrece and Rhae Andrece walking down a street. Roddenberry literally pulled up beside them, jumped out of his car and told them that they were going to be on television!
According to Walter Koenig, NBC considered making a Harry Mudd spin-off show after the success of "I, Mudd." They assigned Gene Roddenberry to develop the idea, but being busy with Star Trek and other projects, he didn't have time for it, and the series was never conceived.
A third-season appearance of Harry Mudd was planned but axed due to the producers' desire to move away from comedy episodes. However, Roger C. Carmel would reprise the role of Mudd as a cartoon voice in Star Trek: The Animated Series: Mudd's Passion (1973). Mudd was considered for a return during the Star Trek movies in the 1980s, but Carmel's failing health nixed that.
The piece of equipment found in Norman's lab and workshop would be recycled for future episodes, appearing in the corridors of the Enterprise. Parts of the device that contained the nanopulse laser were later seen in Dr. McCoy's lab.
David Gerrold did an uncredited rewrite on this episode. One of the significant changes he made, at Gene L. Coon's request, was to get the crew on to the planet by the end of the first act. Other notable contributions were the gag of the five hundred identical female robots, and more material relating to Stella. Coon offered to submit the script for arbitration so that Gerrold would receive credit and residuals. However, Gerrold declined as he felt it would be stealing from Stephen Kandel, who had created Harry Mudd.
Although there are 500 Alice models, we only see fifteen or sixteen. In order of appearance, they are: 1, 2, 66, 99, 19, 263, 118, 322, 471, 210, 27, 11, 3, 73 and 500. The number of the Alice that throws Scott into Kirk's group is too far away to read (although is does seem to be a double-digit figure.)
While searching for identical twins to play androids, casting director Joseph D'Agosta found two young girls (apparently prostitutes) walking on Hollywood Boulevard with their pet wild cat, Marlon. He brought the two girls to meet producer Gene L. Coon and associate producer Robert H. Justman. While they inspected the girls (who were ultimately deemed unsuitable for the role), Coon had to hold Marlon, which consequently scratched him with its claws and tore his entire shirt.
The first draft of the script devoted more attention to Norman's act of diverting the Enterprise to Mudd, with the crew only arriving at the end of the second act. After an examination revealed Norman as an android, Scotty expressed an urge to take Norman apart - quickly adding that it was "nothing personal." Norman understood.
At the end, when Mudd is reviewing the various androids (before the appearance of the Stella androids), two female androids in green dresses appear to be wearing the same dress as Ruth (Maggie Thrett) in Star Trek: Mudd's Women (1966).
Using identical twins for each android "series" aided the photographic-effects budget for the episode. With imaginative use of twins and split screens, as many as six of one model were shown at once, while two of the same model required nothing but an additional costume. This ultimately gave the illusion of a planet of thousands of androids.
This episode marks one of four times Kirk is able to "talk a computer to death". This skill is also used in "The Changeling", "The Return of the Archons", and "The Ultimate Computer" (with an honorable mention going to "What Are Little Girls Made Of?", in which Kirk's arguments get Ruk the android so riled up he suicidally attacks Korby).
The trivia item below may give away important plot points.
When Scotty finally shows up, the Alice android indicates that he is the last one of the crew to be beamed down to the planet. With a crew of over 400 people, it is never explained how all of them can be present on the planet and yet only the six principles (Kirk, Spock, McCoy, Scotty, Uhura, and Chekov) are the only humans (other than Harry Mudd) visible and working to defeat the androids during the 'incarceration' period.