As a global industry, agriculture requires new chemical materials with novel properties to control stubborn pests such as soil-borne diseases. So, Virkon^® S disinfectant that contains oxone (potassium peroxymonosulfate) and sodium dodecyl benzenesulfonate was tested. The study investigated Virkon S nematicidal activity against root-knot nematode (RKN), Meloidogyne incognita, given the lack of data. Egg hatching inhibition was more significant than 50% after one hour of egg masses exposure at a concentration of 0.4% (w/v) in Petri dishes. Virkon S can disintegrate gelatinous egg masses, generating tiny clusters that soon transform into free eggs with a high hatching reduction during embryonic development. Second stage juveniles (J2s) showed exceptional hyperactivity and excitation after less than an hour of exposure before becoming paralyzed, where 1% (w/v) concentration obtained 99.20% mortality after 12 h. Virkon's toxicity increased with concentration, followed by a short latency period, especially against eggs. Virkon S's significant nematicidal activity was evident following tomato J2s inoculation. Virkon S increased fresh root and shoot weight parameters with an increasing percentage directly proportional to applied concentrations 60 days post-application. Virkon S reduced the numbers of J2s and eggs and soil RKN reproduction at various concentrations. Additionally, all Virkon S concentrations had the least galls and egg masses/root, with the concentration of 1% having the most significant reduction in reproduction factor. Increasing the applied concentration through soil drenching led to increases in total sugar, protein, phenolic, and flavonoid content and antioxidant activity, as well as a reduction in nitrate and oxidative enzyme activities in tomato roots with no observed phytotoxic effect on plants; however, foliar spraying with concentrations greater than 0.5% (w/v) caused local leaf scorch injury, developed with 3% (w/v) concentration to plant top death and growing side buds below the damaged area. Finally, the nematicidal activity of Virkon S has been approved, but more studies are needed to eliminate its limited use in plant production.