If you’re driving, U.S. 41 (the Tamiami Trail) runs the length of the region. Sanibel Island is accessible from the mainland via the Sanibel Causeway (toll $6 round-trip). Captiva Island lies across a small pass from Sanibel's north end, accessible by bridge.
Be aware that the destination's popularity, especially during winter, means traffic congestion at peak times of day. Avoid driving when the locals are getting to and from work and visitors to and from the beach.