World Cup-winner Lewis made 223 appearances and won two Heineken Cups and seven Premiership titles during a glittering career at Welford Road and is now an ambassador for Crohn's and Colitis UK.
Lewis will join 30,000 runners at the race start, including Tigers fan Amanda Mealing and many other members of the Tigers Family.
Lewis said: "The London Marathon is something I have always wanted to do.
"I am incredibly proud to be running in aid of such a great charity, which is very close to my heart as I am an Ulcerative Colitis sufferer".
Amanda, who has recently reprised her role as Connie Beauchamp in the popular BBC1 drama series Casualty, is running her third London Marathon in aid of Breast Cancer Care, a charity for which she is an ambassador.
"You can't beat running alongside 36,000 other men and women on those crowded London streets," she recently blogged in the Huffington Post. "And as you run, you feel this incredible strength as the crowd cheer you on to that finish line on The Mall."