The 6ft 4in actor admitted that babies don't like him because of his "gigantic" height.
He told New York Magazine: "They just start crying instantly. I don't know how to hold them or anything. I hold them like the Abominable Snowman from the Bugs Bunny cartoon, like, 'I'll hug you and squeeze you'. I'm like Lenny from Of Mice and Men."
Segel's Marshall is married to Lily (Alyson Hannigan), with the pair expecting a baby in the sitcom.
When asked how he would handle having a baby in the show, Segel said: "I'm going to let her hold the baby most of the time.
"I'm very excited that our hours might be shorter, because you can only work a baby for so long. Because it's a baby. It doesn't even know it's acting."
Segel will make his hosting debut on Saturday Night Live this Saturday.
Segel's revival of The Muppets will be released to theatres in the US on November 23, and on February 17, 2012 in the UK. Segel has said that filming The Muppets was "a dream come true".
Watch the trailer for The Muppets below: