Aims: Melon Manis Terengganu, MMT is one of the economically important fruits in Terengganu, which contains numerous nutritional values and bioactive compounds that benefit human health. The major problem is MMT has been affected by Fusarium sp., which is the common fungus in the Cucurbitaceae family resulting in Fusarium wilt disease and lowering melon production. It may also affect the antioxidant value of MMT; however, limited study has been conducted on this issue. Hence, the objective of this study was to determine the non-enzymatic as well as enzymatic activities in response to Fusarium sp. (S2 and S4) infection. Methodology and results: In this study, MMT leaves were incubated in culture filtrate (CF) obtained from Murashige and Skoog (MS) liquid medium. The antioxidative responses were assayed at 0, 1, 3, 5, 7 and 9 days of treatment. In response to Fusarium infection, the ascorbic acid, α-tocopherol and carotenoid content were significantly stimulated at the early stages of the experiment and slowly reduced afterward. This current study also demonstrated that the CAT-specific activities were initially induced in S2 CF-treated leaves. Similar APX and gPOD specific activity patterns were observed in both S2 and S4 CFs treatments. The APX and gPOD-specific activities were induced at the later stages of infection in S4 CF-treated leaves. Conclusion, significance and impact of study: The results revealed that enzymatic and non-enzymatic antioxidants worked together to fight against stress caused by the fungal infection, with the activation of the plant defense system.