The endophytic Streptomyces enissocaesilis OM182843 was investigated for its antagonistic activity against root-knot nematode (Meloidogyne incognita) as well as its ability to produce plant growth regulators. The nematicidal activity was performed using both culture and crude culture filtrate (CCF) of Strep. enissocaesilis. Both caused high mortality and inhibition of egg-hatching of M. incognita during all experimental intervals. Hydrolytic enzymes (chitinases, proteases and gelatinase), as well as plant growth regulators (indole acetic acid, gibberellic acid, salicylic acid, and proline), were produced by Strep. enissocaesilis in considerable quantities. Furthermore, volatile organic compounds (VOCs) released by Strep. enissocaesilis were analyzed by GC/MS and several of them were found to have nematicidal activity, the most abundant being 2,4-Decadienal, (E, Z) (CAS). This study opens new horizons for thinking about the use of microorganisms to combat pathogens such as root-knot nematodes, which avoid the harmful effects of synthetic nematicides, not only this but also can stimulate plant growth and thus provide a double benefit.