Besides protection, the variability of assemblages in a marine reserve can result from the geographical features of the locations. Islands present within a marine protected area (MPA) offer an extremely valuable system to test the hypotheses of large-scale spatial patterns in assemblages, particularly when patterns on the islands were contrasted with those of the mainland. In fact, besides the natural causes of variability, insular locations are generally less accessible to humans than those on the mainland, with changing levels of accessibility, on the basis of the distance from the coast. This study examined the interactive effect of protection and geographical siting at Tavolara–Punta Coda Cavallo MPA in Sardinia, Italy, on gastropod species subjected to human harvest. Rocky-shore gastropod assemblages were sampled at locations with different level combinations of protection and accessibility. Results highlighted that assemblages in the MPA have been more significantly influenced by the geographical siting of the locations rather than by protection, as the larger dissimilarities were observed between the mainland and island locations. These results can have important implications for the conservation of marine coastal assemblages, and provide important quantitative information for future estimation of the effects of protection of MPAs. Further, they indicate that the inclusion of representative assemblages within the MPA systems requires targeting rocky shores both on the mainland and on islands, thus providing important tools to improve conservation strategies.