An aqueous crude extract from Solanum nigrum lyophilized leaves was evaluated for its phytochemical composition and antifungal activity against Penicillium digitatum, the causative agent of green mold of citrus fruit. Phytochemical analysis of the extract revealed the presence of some bioactive substances such as alkaloids, tannins, flavonoids, saponins, etc. The extract showed a remarkable inhibition zone against the pathogen in agar well diffusion assays carried out in Petri plates. Storage of the extract at 4 °C for 60 days had no effect on its in vitro antifungal activity. Further, the extract was tested for its in vivo (preventive- and curative treatments) antifungal activity on lemons wound-inoculated with P. digitatum. An important preventive antifungal effect was observed after 7 days of storage (100% of inhibition), although this activity decreased after 14 and 21 days (85.71 and 57.14% of inhibition, respectively). A slight curative antifungal activity was observed only after 7 days of storage (14.29% of inhibition). Preliminary findings from this study may contribute to the development of new antifungal agents to protect the lemon fruits from postharvest fungal diseases.