One of the most vital regulatory mechanisms influencing the functional capacity of genes is alternative splicing (AS). Previous studies exploring the splicing landscape of human tissues have shown that AS has played a key role in human adaptation, especially in disease progression and the immune response. Nonetheless, this phenomenon remains uncharacterised in most global populations. One notable region is the Indonesian archipelago, the world's fourth largest nation by population. Despite recent efforts, very little is understood about the complex gene regulatory mechanisms driving the observed diversity across the region. Here, we use a representative set of 115 Indonesian samples from three traditional island populations spanning the genetic ancestry cline that characterises the region (the Mentawai from western Indonesia, the people of Korowai from western New Guinea, and the Sumba population from eastern Indonesia). I conducted a global AS analysis between islands to ascertain the degree of functionally significant AS events and their consequences. Using a hierarchical event-based statistical model, I detected 162 (Mentawai vs. Sumba), 359 (Korowai vs. Mentawai), and 483 (Korowai vs. Sumba) significant AS events, consistent with the previously profiled gene expression differences between these groups. An immune signature was detected across these events, with host-virus interaction genes such as CENPU, LGALS9, GYPA, and IFIH1 being implicated, suggesting differential immune pressure between these islands. Of all AS events, 32% were found to be regulated by RNA binding proteins involved in splicing regulation and mRNA stability. Moreover, 18% of these splicing events influenced transcripts’ coding potential and protein domains. I then sought to identify genetic variants associated with changes in splicing (sQTLs). A total of 7,369 sQTLs and 4,905 unique SNPs were detected across 2,039 genes. Overall, these results contribute towards elucidating the genetically driven gene regulatory mechanisms that shape one of the most diverse regions of the world.