Rice (Oryza sativa L.) is one of the most widely grown crops in the world, and is a staple food for more than half of the global total population. Root-knot nematodes (RKNs), Meloidogyne spp., and especially M. graminicola, seem to be significant rice pests, which makes them the most economically important plant-parasitic nematode in this crop. RKNs develop a feeding site in galls by causing host cells to differentiate into hypertrophied, multinucleate, metabolically active cells known as giant cells. This grazing framework gives the nematode a constant food source, permitting it to develop into a fecund female and complete its life cycle inside the host root. M. graminicola effector proteins involved in nematode parasitism, including pioneer genes, were functionally characterized in earlier studies. Molecular modelling and docking studies were performed on Meloidogyne graminicola protein targets, such as β-1,4-endoglucanase, pectate lyase, phospholipase B-like protein, and G protein-coupled receptor kinase, to understand the binding affinity of Beta-D-Galacturonic Acid, 2,6,10,15,19,23-hexamethyltetracosane, (2S)-2-amino-3-phenylpropanoic acid, and 4-O-Beta-D-Galactopyranosyl-Alpha-D-Glucopyranose against ligand molecules of rice. This study discovered important molecular aspects of plant–nematode interaction and candidate effector proteins that were regulated by M. graminicola-infected rice plants. To the best of our knowledge, this is the first study to describe M. graminicola’s molecular adaptation to host parasitism.