Matlacha Isles-Matlacha Shores is an unincorporated community and census-designated place (CDP) in Lee County, Florida, United States.

It is part of the Cape Coral-Fort Myers, Florida Metropolitan Statistical Area.

Matlacha Isles-Matlacha Shores is located in western Lee County at 26°38′10″N 82°3′46″W / 26.63611°N 82.06278°W / 26.63611; -82.06278 (26.636214, -82.062766),[4] on the east side of Matlacha Pass, a tidal waterway separating Pine Island and Little Pine Island from the mainland.

Southwest Pine Island Road (County Road 78) runs through the community, leading east 12 miles (19 km) to North Fort Myers and west across Matlacha Pass onto Little Pine Island.

The racial makeup of the CDP was 99.01% White, 0.33% Native American, 0.33% Asian and 0.33% Pacific Islander.