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Root-knot nematode is one of the major problems that face the agricultural production of several vegetable crops. Chemical nematicides have been banned because of their healthy and environmental undesirable attributes. So, this study aimed to evaluate the potential use of sweet annie (Artimisia annua) and garden cress (Lepidium sativum) as green routes for the development of effective and eco-friendly alternative nematicides. Nematicidal activity of sweet annie and garden cress aqueous extracts (500 g/L) in the original and nano-forms were evaluated against Meloidogyne incognita in tomato planted in infected soil under greenhouse conditions. Nineteen phenolic compounds were identified in A. annua extract, which was dominated by chlorogenic acid (5059 µg/100 mL), while 11 compounds were identified in L. sativum extract, that dominated by p-hydroxybenzoic acid (3206 μg/100 mL). Nano-particles were characterized with smooth surface, spherical shape and small size (50–100 nm). Under laboratory, the nano-formulations showed mortality percentage of M. incognita J2 greater than the original extract from. Vegetative growth parameters of tomato plants treated with A. annua and L. sativum extracts significantly improved compared to the control plants. Also, biochemical analysis revealed that the extracts were able to induce tomato plants towards the accumulation of phenolic compounds and increasing the activity of defensive enzymes (protease, polyphenol oxidase and chitinase) resulting in systemic resistance. Regarding tomato fruits yield and quality, the studied treatments significantly improved the yield and physicochemical parameters of tomato fruits in terms of fruit weight, diameter, TSS, pH, lycopene content and color attributes gaining higher sensorial acceptance by the panelist. Generally, both extracts represent promising nematicide alternatives and have potential use in crop management. The nano-form of A. annua extract outperformed the nematicidal activity of other studied treatments.