Anthonotha macrophylla, a plant with extensive ethnomedicinal uses, has various parts attributed to healing properties. The bark treats venereal diseases while roots ease intestinal discomfort. Gum extract from the bark provides pain relief, and the leaves are used for ailments like gonorrhea, diarrhea, and malaria. Additionally, the leaves are believed to enhance sexual behavior. Although the age-long folkloric use of Anthonotha macrophylla leaf as aphrodisiac in normal female rats was substantiated with scientific evidence, the study did not account for the aphrodisiac activity in the paroxetine-induced sexual dysfunction male rats. This study investigated the aphrodisiac activity of aqueous extract of Anthonotha macrophylla leaves (AEAML) in the paroxetine-induced sexual dysfunction male rats (PISDMR). Forty-two male rats (144.86 ± 1.21 g) were assigned into sijjkkmx groups (A-F). Group A received distilled water only, while PISDMR in Groups B, C, D, E and F received distilled water, 7.14 mg/kg body weight of sildenafil citrate (reference drug), 25, 50 and 100 mg/kg body weight of AEAML once daily for 7 days. Data were analysed using a one-way Analysis of Variance (ANOVA) and Tukey's post-hoc test at a 5% level of significance. AEAML contained 8 mineral elements and 14 amino acids; potassium (368.24 mg/100g) and glycine (352.70 mg/100g) were the most abundant and cadmium (0.01 mg/100g) and histidine (0.70 mg/100g) were the least. Administration of paroxetine prolonged/ increased (p < 0.05) the mount latency (ML), intromission latency (IL), ejaculation latency (EL), post-ejaculatory interval (PEI), and lowered/reduced (p < 0.05) the mount frequency (MF), intromission frequency (IF) and ejaculation frequency (EF). Paroxetine also decreased the weight of the caudal epididymis, seminal vesicle, ventral prostate, testis, levels of dihydrotestosterone (DHT), testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), dopamine, acetylcholine (ACH), nitric oxide (NO), cyclic guanosine mono phosphate (cGMP) and increased the levels of serotonin, γ-aminobutyric acid (GABA), phosphodiesterase 5 (PDE 5) and Acetylcholineesterase (ACHE) of the animals. In contrast, AEAML significantly (p < 0.05) lowered/reduced the paroxetine-induced related increases in the ML, IL, EL, PEI, and prolonged/ increased (p < 0.05) the paroxetine-induced related decreases in the MF, IF and EF. The AEAML also reversed (p < 0.05) the paroxetine-induced related decreases in the weight of the caudal epididymis, seminal vesicle, ventral prostate, testis, levels of DHT, testosterone, LH, FSH, dopamine, ACH, NO, cGMP and the paroxetine-induced related increases in the levels of serotonin, GABA, PDE 5 and ACHE CONCLUSION: AEAML contains aphrodisiac bioactive agents and can be explored as lead drug for MSD in Wistar rats.