Many fungicides used to control plant diseases have not always been friendly to the environment, which has led to the development of a new generation of eco-friendly fungicides. The purpose of this study was to evaluate the antifungal activity of hydroalcoholic Reynoutria sachalinensis extract. A central composite design was employed to optimize the extraction parameters, namely extraction time, ethanol–water ratio, and temperature. The total flavonoid and total polyphenolic contents, as well as the antioxidant capacity of the obtained extracts, were evaluated. The optimal extraction conditions for obtaining an extract from R. sachalinensis leaves consisted of a 70:30 (v/v) ethanol: water mixture as the extraction solvent, a temperature of 60°C, and a sonication time of 5 min. For the stem extract, the optimal conditions were a 55:45 (v/v) ethanol: water mixture, a temperature of 66.82°C, and an extraction time of 10 min. The extracts obtained under these conditions showed an inhibitory effect on the growth of Fusarium oxysporum f. sp. lycopersici. Mixing the two extracts at a 1:1 ratio resulted in higher antioxidant capacity and a slightly stimulatory effect on fungal growth compared to the individual ones. Taking into account the results obtained, the individual extracts may be used to control tomato wilt disease caused by F. oxysporum f. sp. lycopersici.