The 26-year old, who replaced Mardy Fish as the American number one after reaching the final in Houston last week, is planning to enter the singles, men's doubles and mixed doubles events this summer.
He believes that a potential partnership with Williams in the latter of that treble would give the US a great chance of an Olympic medal.
"It's a lot of tennis in a short amount of time but it's a surface I can do well on," he said.
"She's one of the most dominant players of all time. To have her on my team would be a big advantage."
However, Isner has revealed that he isn't the only American player who wishes to partner the 13-time Grand Slam champion and joked that he would bribe his close friend to pick him as her partner.
"Serena or Venus Williams would be an ideal partner for the mixed. I'm good friends with Serena - I might bribe her, send her a gift in the mail!" he added.
Isner is currently at a career-high world number nine in the ATP rankings.