Tartary buckwheat is one of the nutritious minor cereals and is grown in high-cold mountainous areas of arid and semi-arid zones where drought is a common phenomenon, potentially reducing the growth and yield. Melatonin, which is an amphiphilic low molecular weight compound, has been proven to exert significant effects in plants, under abiotic stresses, but its role in the Tartary buckwheat under drought stress remains unexplored. We evaluated the influence of melatonin supplementation on plant morphology and different physiological activities, to enhance tolerance to posed drought stress by scavenging reactive oxygen species (ROS) and alleviating lipid peroxidation. Drought stress decreased the plant growth and biomass production compared to the control. Drought also decreased Chl a, b, and the Fv/Fm ratio by 54%, 70%, and 8%, respectively, which was associated with the disorganized stomatal properties. Under drought stress, H2O2, O2•−, and malondialdehyde (MDA) contents increased by 2.30, 2.43, and 2.22-folds, respectively, which caused oxidative stress. In contrast, proline and soluble sugar content were increased by 84% and 39%, respectively. However, exogenous melatonin (100 µM) could improve plant growth by preventing ROS-induced oxidative damage by increasing photosynthesis, enzymatic antioxidants (superoxide dismutase, peroxidase, catalase, and ascorbate peroxidase), secondary metabolites like phenylalanine ammonialyase, phenolics, and flavonoids, total antioxidant scavenging (free radical DPPH scavenging), and maintaining relative water content and osmoregulation substances under water stress. Therefore, our study suggested that exogenous melatonin could accelerate drought resistance by enhancing photosynthesis and antioxidant defense in Tartary buckwheat plants.