The fragmentation of traditional multilateral institutions and intensifying geopolitical competition are reshaping the global order, placing unprecedented pressures on small and medium-sized states, particularly across the Global South. This article explores ‘minilateralism’ as an adaptive strategy employed by these states to protect sovereignty, foster resilience, and assert agency amid systemic uncertainty. Through a comparative analysis of three regional minilateral initiatives – the Indonesia–Malaysia–Thailand Growth Triangle (IMTGT), the Pacific Islands Forum (PIF), and the Alliance of Sahel States (AES) – the study examines the varied trajectories, institutional evolutions, and diplomatic innovations that characterize sovereignty-conscious minilateralism. It challenges prevailing assumptions that portray minilaterals as transient or externally dominated, demonstrating instead their role as durable, strategic instruments for smaller states. The article concludes with lessons for theoretical development and practical policymaking, emphasizing the importance of tailoring minilateral designs to regional realities, strategically leveraging sovereignty, and complementing minilateral initiatives within broader multilateral frameworks. The analysis finds that minilateral frameworks in the Global South enable small and medium-sized states to assert sovereignty, navigate geopolitical pressures, and create durable alternatives to traditional multilateralism.