Root-knot nematodes, Meloidogyne spp., are obligate endoparasites with major global economic significance. Their reproductive techniques display a broad variety continuum, ranging from amphimixis to obligatory mitotic parthenogenesis. Root-knot nematodes (RKN) developed invasion and colonization techniques, including the expression of immune suppressors to get beyond the host plant’s defences. Natural products are used to combat these potentially dangerous microorganisms as part of sustainable agriculture, which strives to regulate soil and plant health while using fewer chemical inputs. Most of these natural products are biodegradable, and their investigation is subject to less-stringent regulatory approval procedures. In this study, we provide an extensive overview of the biological control of Meloidogyne and the main mechanisms of action of plant products against RKN. We discussed the different nematicidal activities imposed by natural products alongside their large-scale efficiency in controlling RKN. Finally, we provide an overview of the major factors affecting the success or failure of using natural products as a reliable strategy to control RKN.