Goddard will join the Saints as a development coach and Misson will have a liaison role between coaching, high performance and medical staff at the club.
Fellow Saints star Lenny Hayes had returned to the club as an assistant before last month's bombshell decision to sack coach Brett Ratten, less than 100 days after St Kilda had re-signed him.
The Saints signed Lyon less then a fortnight later, and a day after that two-time Brownlow Medal winner Robert Harvey joined them as an assistant coach.
Nick Dal Santo, another former Saints star, coaches their AFLW team.
Goddard played 205 games for St Kilda between 2003 and 2012, and was a key member of the teams that made the 2009-10 grand finals under Lyon.
He finished his career with 129 games at Essendon, including the captaincy in 2016, for a career total of 334.
Misson, as head of conditioning, was one of Lyon's key lieutenants in his first spell as St Kilda senior coach.
He wrote a book about his time at the club, called The Bubble, which referred to the "us against the rest" mentality that pervaded the club in the Lyon regime.
Misson has also worked at AFL rivals Sydney and Melbourne, as well as with the Australian cricket team and, most recently, the Roosters in the NRL.
"His ability to maximise the physical potential of an athlete and contribute to overall high performance goals of an organisation is unmatched, and we are excited to have someone of his calibre in our program," new Saints football boss Geoff Walsh said.
"David will work across all areas of our program, particularly with head of performance and conditioning Nick Walsh, and the physio and medical staff.
"Brendon also has clear passion for the growth of this club, having played over 200 games in the red, white and black.
"A quality player throughout his career, Brendon has been honing his coaching skills in the VAFA and we're pleased to be welcoming him to the program to assist Damian Carroll with our player development."
Goddard and Misson will return to the Saints officially on November 7.
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