Marine mollusks are a prolific source of secondary metabolites with complex/diverse structures and various aspects of biological activities. For the above-mentioned reason, these animals have been extensively explored and have become the hotspot of the research subject in recent years. It is well documented that mollusks can escape from predation by utilizing bioactive metabolites as defensive chemicals. In the last decade, the possible diet relationship between the South China Sea mollusks and their related potential prey organisms, including sponges, corals, algae, etc. has been systematically investigated. A series of interesting results have been obtained concerning the chemistry, chemoecology, and pharmacological profiles of the studied marine organisms. The present review focuses on recent developments dealing with chemistry, chemoecology, and bioactivity of the South China Sea mollusks and their dietary organisms.