Muthusamy played the last of his three tests in March 2023 and joins Keshav Maharaj and Dane Piedt as the specialist slow-bowling options in the squad.
"We have three frontline spinners and all of them have the ability to step up at any time they are needed," South Africa coach Shukri Conrad said.
"This is a great chance for someone like Senuran, who has the potential to make a mark with both bat and ball."
Batter Matthew Breetzke is the only uncapped player in the squad, though he did tour West Indies in June when South Africa won a rain-affected series 1-0.
Cricket South Africa released a statement earlier on Monday confirming the tour would go ahead following a security review.
Bangladesh has seen deadly protests that led to the ousting of Prime Minister Sheikh Hasina last month.
"A security assessment was recently conducted by CSA's Operations Manager, Team Security Manager, Safety and Security Consultant, and a representative of the South African Cricketers’ Association," CSA said.
"CSA has given the series a go-ahead based on the recommendations made by the team post an in-loco inspection visit to Bangladesh."
Temba Bavuma will captain the side with the first test in Dhaka from October 21st - 25th and the second in Chattogram from October 29th - November 2nd.
Squad: Temba Bavuma (captain), David Bedingham, Matthew Breetzke, Nandre Burger, Tony de Zorzi, Keshav Maharaj, Aiden Markram, Wiaan Mulder, Senuran Muthusamy, Dane Paterson, Dane Piedt, Kagiso Rabada, Tristan Stubbs, Ryan Rickelton and Kyle Verreynne
