Abstract: The red palm weevil (RPW), Rhynchophorus ferrugineus (Oliv.) is ranked as a category-1 pest of date palms in the Gulf Region and causes huge economic losses to the date producing community. This study performs the differential proteomic analysis of date palm leaves associated with RPW infestation by using two-dimensional differential gel electrophoresis (2D-DIGE) to identify the potential molecular marker for early detection of RPW. The results indicated quantitative changes in the expression profiling of leaf proteome between control and RPW infested samples. In total, 32 differentially expressed spots specific to RPW infestation were recorded (p ≤ 0.05 having ≥ 1.5-fold modulation). These differently expressed proteins were analyzed with Matrix-Assisted Laser Desorption/Ionization- Time of Flight (MALDI-TOF-TOF) mass spectrometer for their identification and characterization. Protein related to stress/defense, photosynthesis, carbohydrate utilization system and protein degradation revealed up or down regulations in the infested samples. These differentiallyexpressed peptides can be used as a biomarker for the detection of RPW infestation in date palm at early stages.