Understanding the management of the rice root-knot nematode Meloidogyne graminicola is an essential component of rice. The study aimed to investigate the extent to which the nematicidal actions of 2,1,3- benzothiadiazole, fluopyram, fluensulfone and carbofuran against the rice root-knot nematode, M. graminicola could be determined using in vitro, in vivo and in silico studies. Among the tested compounds, fluopyram demonstrated the highest juvenile mortality rate (91.26%) and binding affinity (-8.3 kcal/mol) to the seven selected target proteins of M. graminicola, driven by significant hydrophobic, alkyl and H-bonding interactions. Comparative binding affinities were recorded for fluensulfone (-6.9 kcal/mol), carbofuran (-6.4 kcal/mol), 2,1,3-benzothiadiazole (-5.0 kcal/mol) and untreated control. These findings have significant implications for agricultural practices, particularly in developing integrated pest management (IPM) strategies. The high efficacy of fluopyram, as evidenced by its biochemical ligand-target protein interactions, suggests its potential as a key component in IPM programs. By integrating nematicidal treatments with other control measures such as crop rotation, resistant rice varieties and biological control agents, sustainable management of M. graminicola can be achieved by reducing dependency on chemical pesticides. Furthermore, this study underscores the importance of using molecular insights to design targeted pest management solutions, paving the way for environmentally responsible and economically viable approaches to nematode control in rice cultivation.