Objective: To investigate the physiological and biochemical effects of incompatibility between Khatooni melon (Cucumis melo GR. Inodorus accession Khatooni) scion on cucurbit rootstocks, a series of experiments was conducted in a randomized complete block design at the Horticultural Research Station of the University of Tehran in Mohammadshahr, Karaj, in 2021.Methodes: Seven different Cucurbit Rootstocks were applied in this research, which include: 'Rout Power', 'ES 900', 'RZ 12', 'Nongwoo 01', 'RZ6' 'Shintozwa', 'Marvel' and the seed rootstock of the melon cultivar 'Khatooni' with the scientific name (Cucumis melo GR. Inodorus accession Khatooni) was also used as a control plant in addition to the scion. Then the effects of incompatibility and compatibility on the yield of fruit weight, number of fruit and marketable yield were checked. Then biochemical activity of plant scion, such as sugar and starch content of scion leaves, leaf mineral elements (N, P, K, Ca, Mg, B) and the amount of stress proteins and enzymes super oxide dismutase, peroxidase and catalase (SOD, PO, CAT) were compared.Results: Variance analysis revealed significant differences (p<0.01) among treatments in yield traits, stress enzyme activities, protein, and carbohydrate content. Elements such as nitrogen, potassium, calcium, and boron showed significant variation at the 5% level. The highest fruit weight, number of fruits, and marketable yield were observed with Rout Power and Shintozwa rootstocks, indicating incompatibility compared to the Marvel rootstock. Protein accumulation at the graft junction was 1.03 mg/fresh weight in incompatible Marvel rootstocks versus 0.6 mg in Shintozwa, which was more compatible. Higher antioxidant enzyme activities were found in incompatible rootstocks. Sugar and leaf starch contents were higher in Shintozwa relative to incompatible rootstocks, while leaves of compatible plants showed significantly greater levels of N, Ca, Mg, and B.Conclusion: Rootstock incompatibility adversely affects physiological and biochemical growth traits and scion performance. The Marvel rootstock exhibited incompatibility, whereas Shintozwa demonstrated compatibility with the Khatooni melon scion. Therefore, Shintozwa is recommended as a suitable rootstock for melon grafting to ensure optimal growth and yield