High temperature and drought stress often occur simultaneously, and due to global climate change, this kind of phenomenon occurs more frequently and severely, which exerts devastating effects on plants. Polyamines (PAs) play crucial roles in conferring abiotic stress tolerance in plants. Present study investigated how exogenous pretreatment of spermine (Spm, 0.2 mM) enhances mung bean (Vigna radiata L. cv. BARI Mung-2) seedlings tolerance to high temperature (HT, 40 °C) and drought [induced by 5 % polyethyleneglycol (PEG)] stress individually and in combination. Spm pretreatment reduced reactive oxygen species (ROS) production including HO and O, lipoxygenase (LOX) activity, and membrane lipid peroxidation (indicated by malondialdehyde, MDA) under HT and/or drought stress. Histochemical staining of leaves with diaminobenzidine and nitro blue tetrazolium chloride also confirmed that Spm-pretreated seedlings accumulated less HO and O under HT and/or drought stress. Spermine pretreatment maintained the ascorbate (AsA) and glutathione (GSH) levels high, and upregulated the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), dehydroascorbate reductase (DHAR), and glutathione reductase (GR) which were vital for imparting ROS-induced oxidative stress tolerance under HT and/or drought stress. The cytotoxic compound methylglyoxal (MG) was overproduced due to HT and/or drought, but exogenous Spm pretreatment reduced MG toxicity enhancing the glyoxalase system. Spermine pretreatment modulated endogenous PA levels. Osmoregulation and restoration of plant water status were other major contributions of Spm under HT and/or drought stress. Preventing photosynthetic pigments and improving seedling growth parameters, Spm further confirmed its influential roles in HT and/or drought tolerance.