ABSTRACTPlant growth regulators (PGRs) improve crop growth and mitigate the adverse effects of drought stress. This study explores the effects of various PGRs including melatonin (MT), indole‐butyric acid (IBA) and gibberellic acid (GA3) on drought‐tolerant Zhongzhe 9 (ZZ9) and Xintaitang 22 (ROC22), as well as drought‐sensitive varieties Guitang‐44 (GT44) and Funong 41 (FN41) varieties. A pot experiment was conducted to evaluate the foliar application of these hormones alone or in combination on sugarcane seedlings under drought stress conditions. At the sixth leaf stage, drought stress was induced by reducing soil moisture to 40%–45% field capacity. Results showed that the drought‐sensitive variety GT44 had the highest plant height (17.97 cm), while PGRs application enhanced the relative water content (RWC) in FN41 by 0.96%. PGRs treatment also increased plant height by 33.98% and RWC by 3.26% compared to controls. MT application significantly increased chlorophyll a and b contents in FN41 by 4.82% and 4.51%, respectively. Antioxidant enzyme activities superoxide dismutase and peroxidase increased by 16.39% and 12.57%, respectively, indicating enhanced oxidative stress defence. Moreover, PGRs applications reduced hydrogen peroxide and malondialdehyde (MDA) accumulation, signifying decreased oxidative damages. The combinations of MT + GA3 and MT + IBA + GA3 significantly improved the plant growth attributes, antioxidant enzymes, osmolytes and reduced the accumulation of ROS and MDA content in both tolerant and sensitive varieties under drought stress. Thus, combined application of MT + GA3 and MT + IBA + GA3 treatments effectively mitigated drought stress in sugarcane seedlings, providing valuable insights for sustainable agricultural practices.