Malaria remains a leading cause of morbidity and mortality among children under 15 years of age in Nigeria, highlighting the urgent need for effective and affordable antimalarial agents. Mangifera indica L. (mango) is traditionally used in malaria management; however, its in vitro efficacy against Plasmodium falciparum requires systematic evaluation. This study investigated the antimalarial activity of aqueous and ethanolic extracts of M. indica leaves and stem bark against P. falciparum isolates obtained from children attending the Federal Medical Centre, Jalingo, Taraba State, Nigeria. Plant materials were air-dried, pulverized, and extracted by cold maceration using distilled water and ethanol. Qualitative phytochemical screening was conducted to identify secondary metabolites, while quantitative analyses determined the concentrations of alkaloids, saponins, tannins, flavonoids, and phenols. In vitro antiplasmodial activity was assessed using parasitized red blood cells by measuring mean parasitized cell counts, percentage inhibition, and IC₅₀ values across extract concentrations of 1.56–100 μg/mL. Data were expressed as mean ± standard error of the mean (SEM), with statistical significance set at p ≤ 0.05. Phytochemical analysis revealed high saponin content in the aqueous extracts of both leaves and stem bark, and elevated alkaloid levels in the ethanolic stem bark extract (9.66 ± 0.27 mg/100 g). Flavonoids were most abundant in the ethanolic leaf extract (11.24 ± 0.39 mg/100 g), whereas phenols were highest in the aqueous stem bark extract (0.75 ± 0.03 mg/100 g). All extracts produced concentration-dependent reductions in parasitized cells. The ethanolic stem bark and leaf extracts showed the lowest parasitemia levels of 50.00 ± 1.96 and 40.16 ± 4.36, respectively, at 3.13 μg/mL, corresponding to high percentage inhibition (90.44 ± 2.57% and 93.22 ± 2.60%). IC₅₀ values confirmed strong antiplasmodial activity, with ethanolic stem bark and leaf extracts showing IC₅₀ values of 2.63 μg/mL and 2.93 μg/mL, respectively. Combination extracts demonstrated consistent synergistic inhibition across all concentrations tested. These findings indicate that M. indica leaves and stem bark possess potent antimalarial activity and may serve as promising sources for the development of natural antiplasmodial agents.