This study aims to find spatial clusters of diabetes and physical inactivity among a sample population in Kerala, India, and evaluate built environment characteristics within the high and low spatial clusters. Spatial clusters with a higher and lower likelihood of diabetes and physical inactivity were identified using spatial scan statistic at various radii. Built environment characteristics were captured at panchayat level and 1600 m buffer around participant location using Geographical Information Systems. Comparison of sociodemographic and built environment factors was carried out for participants within high and low spatial clusters using t tests. Ten high and 8 low spatial clusters of diabetes and 17 high and 23 low spatial clusters of physical inactivity were identified in urban and rural areas of Kerala. Significant differences in built environment characteristics were consistent for low spatial clusters of diabetes and physical inactivity in the urban scenario. Built environment characteristics were found to be relevant in both urban and rural areas of Kerala. There is an urgent call to explore spatial clustering of non-communicable diseases in Kerala and undo the one-size-fits-all approach for prevention and control of non-communicable diseases.