Small and medium enterprises (SMEs) play a vital role in India’s manufacturing sector but often struggle with quality control, environmental compliance, and global competitiveness. However, they face significant challenges in achieving operational excellence, sustainability, and global competitiveness. This study explores the integration of six sigma methodologies with sustainable bioinspired manufacturing principles to improve performance and minimize environmental impact. Using a literature review and empirical analysis, the study identifies key critical success factors (CSFs) that influence six sigma implementation in Indian SMEs. Statistical analysis shows that CSFs significantly affect performance, offering insights for strategic six sigma adoption. Based on the best-worst method analysis, “selection of the right project” (weight = 0.3287), “employee training” (0.1862), and “infrastructure availability” (0.1076) emerge as the top-ranked CSFs, collectively contributing over 62 % in improving the operational performance of SMEs. This study uniquely contributes by examining the intersection of six sigma and bioinspired manufacturing specifically within Indian SMEs, an area that remains underexplored in the literature. Unlike prior studies that treat these domains separately, the present work investigates how bioinspired design principles can be practically integrated into six sigma’s structured framework to achieve sustainability and quality objectives.