Cotton (Gossypium hirsutum L.) is a multipurpose crop. Abiotic stresses, especially extreme heat and drought, limit crop growth and thus reduce cotton yield by about 50%. In this study, 30 cotton genotypes were tested against low moisture stress in a pot experiment in triplicates along with control under wire house conditions. At the 3–4 leaf stage, different morpho-physiological and biochemical parameters were measured in order to select the low moisture stress-tolerant genotypes. For the selection of the best performing genotypes, Multi-Trait Genotype-Ideotype Distance Index (MGIDI) was used for the ranking of genotypes on the basis of multiple indices. For biochemical traits, 09 (TPC, TF, TSP, MDA, SOD, POD, CAT, APX, and Proline) out of 24 showed significant genotypic effects and were used for MGIDI. Eight genotypes (N-812 N-1296 N-696 N-377 N-121–896 N-T86, and N-3496) were observed to be best performing than others at 25% selection pressure (SI = 25%). For morpho-physiological traits, 14 out of 15 showed significant genotypic effects and used for MGIDI. Ten genotypes (N-1237 N-812 N-1296 N-696 N-9078 N-377 N-512 N-121 N-375, and N-896) were observed to be best performing at 35% selection pressure (SI = 35%). Six genotypes, i.e. N-812–1296 N-696 N-377 N-121, and N-896 were found common in both MGIDI analysis. In conclusion, three genotypes, i.e. N-696, N-896, and N-T86 proved to be most resilient to low moisture stress. Develop protocols, identified genotypes and markers that can be used for development of climate-smart cotton genotypes.