Bio-stimulants, such as selenium nanoparticles and melatonin, regulate melon growth. However, the effects of individual and combined applications of selenium nanoparticles and melatonin on the growth of melon seedlings have not been reported. Here, two melon cultivars were sprayed with selenium nanoparticles, melatonin, and a combined treatment, and physiological and biochemical properties were analyzed. The independent applications of selenium nanoparticles, melatonin, and their combination had no significant effects on the plant heights and stem diameters of Jiashi and Huangmengcui melons. Compared with the controls, both selenium nanoparticle and melatonin treatments increased soluble sugars (6-63%) and sucrose (11-88%) levels, as well as the activity of sucrose phosphate synthase (171-237%) in melon leaves. The phenylalanine ammonia lyase (29-95%), trans cinnamate 4-hydroxylase (32-100%), and 4-coumaric acid CoA ligase (26-113%), as well as mRNA levels, also increased in the phenylpropanoid metabolism pathway. Combining the selenium nanoparticles and melatonin was more effective than either of the single treatments. In addition, the levels of superoxide dismutase (43-130%), catalase (14-43%), ascorbate peroxidase (44-79%), peroxidase (25-149%), and mRNA in melon leaves treated with combined selenium nanoparticles and melatonin were higher than in controls. The results contribute to our understanding of selenium nanoparticles and melatonin as bio-stimulants that improve the melon seedlings' growth by regulating carbohydrate, polyamine, and antioxidant capacities.