Drought stress is a major concern for current agriculture as it limits plant growth and yield. An experiment was conducted with a drought susceptible rice (Oryza sativa L. cv. BRRI dhan29) to explore the potential functions and possible mechanisms of exogenous glutathione (GSH)-induced drought stress tolerance. Fifteen-day-old seedlings, GSH-pretreated or non-pretreated (0.2 mM GSH for 72 h), were subjected to PEG-induced (15% polyethylene glycol 6000) drought stress for 4 days. Rice plants exposed to drought stress displayed reduced growth, which was correlated with reduced chlorophyll content, water balance, antioxidant enzymes activities and mineral contents (K+, Ca2+ and Mg2+), as evidenced by principle component analysis (PCA) and heatmap clustering. The PCA also revealed that hydrogen peroxide (H2O2) and malondialdehyde (MDA) accumulations were strongly linked with the declined growth and development of rice plants under drought stress. Importantly, pretreatment with GSH improved the growth responses of rice plants to drought stress. GSH strengthened numerous physio-biochemical processes which were coupled with increased uptake of K+, Ca2+ and Mg2+, enhanced accumulation of soluble sugars, higher activities of enzymatic and non-enzymatic antioxidants. Moreover, GSH-pretreated seedlings under drought stress conditions had lower levels of O2·− , H2O2 and MDA which indicates successful adaptation of rice seedlings to drought stress. The results of PCA strongly supported that GSH conferred drought tolerance mostly by enhancing antioxidant activities and mineral homeostasis. Collectively, our findings provide an important prospect for use of GSH in modulating drought tolerance in rice plants. Breeding strategies should therefore be undertaken to increase the GSH content of rice plants as a means to increase drought tolerance.