Eighteen guava genotypes from Tamil Nadu, India, were screened for resistance to the root-knot nematode, Meloidogyne enterolobii. The wild guava Psidium eugeniaefolia showed a highly resistant reaction to M. enterolobii, while Psidium cattleyanum var. lucidum was resistant and Psidium guajava cv. Peelamedu Local showed moderate resistance. Other genotypes, Psidium chinensis, Psidium guineense primitive, P. guineense, including Psidium guajava varieties like Allahabad Safeda, Arka Mridula, Taiwan Pink, Lalit, Chittidar, Banarasi, Tiruvannamalai Local 1, Thiruvannamalai Local 2, and Thondamuthor Local exhibited susceptible reactions. Psidium guajava varieties such as. L-49, L-46, and Kenathukadavu Local showed highly susceptible responses. Root exudate analysis from P. eugeniaefolia (highly resistant) identified 12 specific compounds repelling nematodes, while P. cattleyanum var. lucidum (resistant) had no significant effect, and Arka Kiran (susceptible) was attractive to nematodes. In-silico molecular docking analysis suggested that 9(2H)-acridinone, prostaglandin, dimetindene, and 3-pyridinecarboxylic acid, docosahexaenoic acid compounds contributed to resistance by various means such as i) direct killing of juveniles by binding with cuticular collagen, ii) disrupting the nematodes orientation towards the roots and iii) by enhancing host innate immunity against M. enterolobii. A 90 % graft success rate was achieved using P. eugeniaefolia as rootstock for P. guajava cv. L-49, indicating its potential for controlling M. enterolobii in guava cultivation.