Thailand, located in Southeast Asia, boasts a rich marine biodiversity characterized by its extensive coastline and unique marine ecosystems. The country’s marine resources, particularly its diverse sponge species, have drawn considerable interest in natural product research due to their potential in pharmaceutical applications. This chapter focuses on sponge-derived marine natural products (MNPs) identified in Thailand, highlighting their chemical diversity and biological activities. The discussion spans terpenoids, steroids, alkaloids and other bioactive compounds, showcasing their roles in combating infections, cancers and other diseases. Research conducted since 1988 has yielded numerous bioactive compounds from Thai sponges, many of which exhibit potent anti-infective, cytotoxic or antimalarial activities. Significant efforts have been directed towards understanding the chemistry and biosynthesis of these metabolites, including semi-synthetic derivatives, to enhance their therapeutic potential. This comprehensive review not only underscores the pharmaceutical promise of Thai marine sponges but also emphasizes the collaborative contributions of Thai and international research teams in the advancement of marine natural products. The findings presented here pave the way for future drug discovery efforts while advocating for the conservation of Thailand’s unique marine ecosystems.