Background: Infertility is an important issue for couples that may cause various psychological and emotional problems. Female infertility disorders play a major role in approximately 50-80% of the causes of infertility in various areas in Nigeria. Moringa oleifera has been proposed as a plant with female fertility enhancement effects. The objective of this study was to assess the fertility-improving effects of ethanol extract of M. oleifera leaf and to determine the phytochemical components causing these effects by in silico analyses. Methods: The in vitro effects on fertility were evaluated using Drosophila melanogaster (fruit fly) because of its genetic similarities to humans. The copulation duration, mating latency, and the number of emergences from the fruit fly after mating were determined. Three doses (0.025%, 0.05%, and 0.1% w/w) of the M. oleifera ethanol extract were administered to three different groups, while a control group only received feed mixed with ethanol. For in silico studies, 62 compounds were obtained from the PubChem library by mining compounds from articles related to M. oleifera. Next, a ligand library was generated and docked against various targets of interest (estrogen, progesterone, kisspeptin, liver X, PPARG, and 15-PGDH receptors as well as 17β hydroxysteroid dehydrogenase and insulin-degrading enzymes) which have female fertility-enhancing effects. Results: The in vivo experiments showed that M. oleifera had no effect on copulation duration and mating latency, but interestingly, it enhanced the fertility/emergence of the treated fruit flies. In silico studies suggested that phytochemicals such as rutin, marumoside B, myricetin, and quercetin showed docking scores that may well support previous works on M. oleifera enhancement of female fertility. Conclusion: The results showed that M. oleifera can enhance fertility in female fruit flies.