The aim of this work was to study the effects of hydrogen peroxide (H₂O₂) application against cucumber green mottle mosaic virus (CGMMV) infection in watermelon (Citrullus lanatus) plants. From the obtained results, the induced resistance using H₂O₂ treatments caused a delay in the appearance of CGMMV symptoms in watermelon plants. The viral infection showed abnormal morphological symptoms such as mosaics, yellow blisters and reduction in size. Pretreatment with H₂O₂ before infection was beneficial in increasing the contents of pigments, total proteins, total free amino acids and proline. Consequently, plants appeared morphologically similar to healthy controls. Signaling the effect of the H₂O₂ treatment could induce partial resistance or delay the appearance of symptoms and decreased virus concentration. The induced mechanism of resistance was suggested to be through alterations of plant antioxidant status – both enzymatic and non-enzymatic. All analyzed antioxidant enzymes were induced in response to H₂O₂±CGMMV. Due to the H₂O₂ application prior to infection, malondialdehyde (MDA) content was reduced, indicating a lowering in lipid peroxidation caused by virus infection. On the other hand, internal H₂O₂ and phenolics contents were induced in H₂O₂ + CGMMV-treated leaves. To confirm: total antioxidant activity was increased to be double the value (80.67%) of that recorded in healthy plants (47.18%), indicating changes in antioxidant status as a response to H₂O₂ and/or CGMMV infection. This work provided evidence of the signaling role of exogenous H₂O₂, which led to systemic acquired resistance (SAR) induction acting against CGMMV infection in watermelon plants. From the present findings, a suggestion of spraying of H₂O₂ might be helpful in avoiding the appearance of CGMMV severe symptoms throughout the plants’ life.