The group, who have been on an extended break since 2008, will appear at the gala event in Los Angeles.
Further acts including Wilco, Norah Jones and James Taylor have also been confirmed to perform and Neil Young will be honoured as the MusiCares Person of the Year.
Proceeds from the dinner and concert will be donated to MusiCares, which provides support for artists in financial, medical and personal need.
Red Hot Chili Peppers have been working on separate projects over the past year, with singer Flea teaming up with Radiohead's Thom Yorke to form a music supergroup.
The band reportedly started working on new material in October.