Soon after the discovery that phosphodiesterase (PDEs) are presented in nematodes and regulate the signaling pathway responsible for its motility and reproduction, many of PDE inhibitors have been examined for their nematicidal effects. The present study evaluates the nematicidal activity of seven commercial drugs that act as PDE inhibitors namely diazepam, papaverine, theophylline, caffeine, cilostazol, vinpocetine and sildenafil against root-knot nematodes (Meloidogyne incognita) under laboratory and greenhouse conditions. The results showed that all tested PDE inhibitors reduced tomato root galling significantly compared with the untreated check. Diazepam, papaverine and caffeine treatments gave the highest reduction in root galls by 95.5, 93.3 and 91%, respectively.Diazepam exhibited strong nematicidal activity against second-stage juveniles (J2) of M. incognita with 48hrs-LC₅₀ value of 4.63 ppm. Therefore, using phosphodiesterase inhibitors could serve as the basis for novel nematicides with greater efficacy and reduced environmental impact.