Mangrove is one of the most precious ecosystems with the greatest losses due to climate change, human activities, and pollution. The objective of this study is to assess the accumulation and distribution of some trace metals (Cu, Cd, Ni, Pb, and Zn) in sediments and Avicennia marina roots and leaves and to discuss the antioxidant potential of A. marina under metallic pollution stress. Sediments, leaf, and root samples of A. marina were collected from five sites along the Red Sea Coast of Egypt. Several ecological pollution indices, including the geo accumulation index (Igeo), contamination factor (CF), pollution load index (PLI), bioconcentration factor (BCF), and translocation factor (TF), were used to assess the pollution load. Cu, Cd, Ni, Pb, and Zn average concentrations in sediments were 167.4, 0.75, 110.65, 39.79, and 220 μg g−1, respectively, and the average values of these metals in A. marina roots were 44.9, 0.5, 87.96, 39.02, and 54.68 μg g−1, respectively, while in leaves their concentration were 50.46, 0.5572, 88.24, 40.08, and 56.08 μg g−1, respectively. The values of the Igeo, CF, and PLI index indicated that location 1 and 5 are moderate-to-heavily contaminated sites. On the other hand, leaves and roots of A. marina grown in polluted locations 1 and 5 showed high accumulation of malondialdehyde (MDA), low chlorophyll a and chlorophyll b contents concomitant with a decrease in total soluble sugars. High total antioxidant capacity was associated with a significant increase in activity levels of antioxidant enzymes (Catalase, Polyphenol oxidase, Polyphenol peroxidase, and Ascorbic acid oxidase), accumulation of secondary metabolites (total phenols, flavonoids, and tannins), and proline and carotenoids content increase. Overall, the present study suggests that the mangrove habitat of the Egyptian Red Sea coast is under the stress of anthropogenic activities, which necessitates a conservation plan to avoid further contamination and protect the unique biota of this distinctive habitat.