To counter the insect infestation, plants respond with wide-ranging and highly dynamic biochemical reactions. Of these, the anti-oxidative activity is poorly understood. The red palm weevil (RPW) Rhynchophorus ferrugineus (Oliver), one of the most widespread pests in Pakistan, prefers to infest date palm Phoenix dactylifera. Our present study investigated the feeding preference of RPW to 11 different date palm cultivars and the results suggested that the Hillawi cultivar was most preferred. Greater infestation rate, fecundity and hatching rate were also recorded from Hillawi and Mozawati than other cultivars. No significant decreases were observed in chlorophyll a, chlorophyll b, total chlorophylls and carotenoids of RPW-infested Hillawi cultivar over un-infested control. In contrast, the contents of enzymatic antioxidants including phenols, proline, hydrogen peroxide, anthocyanin, malondialdehyde, ascorbic acid and glycine betaine showed a drastic increase after RPW infestation, and there was enhanced superoxide dismutase, peroxidase and catalase activities. Furthermore, we recorded the increase of total protein and sugar contents in RPW-infested date palms. These findings offer valuable insight into the antioxidative molecular mechanism of date palms under RPW attack and may contribute to the breeding of insect-resistant crops.