The interaction between endophytic fungi and phytochemicals in the dominant mangroves (Rhizophora mangle, Lacugularia racemosa, and Avicennia africana) of the Iko River Estuary in Nigeria was investigated. Standard analytical procedures were employed to measure antioxidant levels, while endophytic fungi were isolated, morphologically characterized, and identified using culture-dependent methods. The study identified various bioactive compounds, including alkaloids, saponins, tannins/phenols, flavonoids, deoxy-sugars, cardiac glycosides, and steroids, with their concentrations varying depending on the mangrove species and plant parts. Alkaloids were present in all mangrove samples, with particularly high concentrations in the leaves of white (5%) and red (4.2%) mangroves. Principal Component Analysis (PCA) was used to analyze the interaction between the endophytic fungi and phytochemicals, revealing a distinct affinity of certain fungal species for specific antioxidants in the mangroves. Fungal species such as Phoma sp., Rhizopus arrhizus, Aspergillus niger, and others exhibited a negative relationship with tannins, flavonoids, deoxysugars, and cardiac glycosides, but a positive affinity for saponins, alkaloids, and steroids. Conversely, Candida pseudotropicalis, Fusarium oxysporum, P. italicum, and others showed a positive affinity for tannins, flavonoids, cardiac glycosides, and deoxysugars, but a negative affinity for alkaloids, saponins, and steroids. Notably, Absidia sp. was the only frequently isolated species with a strong correlation (r value ≥75 at a 95% confidence limit) with deoxy-sugars, while Aspergillus niger, Aspergillus terreus, and Absidia sp. demonstrated significant relationships with alkaloids, saponins, and steroids. These phytochemicals, which serve as precursors to antioxidants with promising biotechnological applications, likely play a crucial role in determining the association of endophytic fungi with deltaic mangroves in Nigeria.