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Calotropis procera (Aiton) Dryand (commonly known as the apple of sodom, calotrope, and giant milkweed) is an evergreen, perennial shrub of the Apocynaceae family, and is mainly found in arid and semi-arid regions. Previous studies have established the toxic effects of Calotropis procera (C. procera) (Aiton). Its extract is used as one of the vital alternatives to pesticides due to its effective impacts on several pathogens and to combat insect pests that cause severe damage to several crops, but so far, its effects on combating Fusarium oxysporum f. sp. lycopersici (FOL) have not yet been evaluated. Therefore, the current study focuses on evaluating the effects of the aqueous extract of this plant on FOL by studying physicochemical indicators. In Saudi Arabia and many other countries, such disease is considered as one of the critical factors affecting tomato growth and production. For the control of Fusarium wilt disease (Fwd), many strategies have been developed, but are limited in their use. Ten isolates of the pathogens were obtained from diseased tomato plants. These isolates were able to exhibit symptoms of tomato wilt, and they varied in their virulence. Isolate No. 5 caused the highest severity of the disease (73%). According to these results, we used this isolate in the following experiment, which was identified by ITS sequences as F. oxysporum f. sp. lycopersici. Following intensive screening studies, we selected aqueous plant extract of C. procera to study its effectiveness against Fwd of tomato plants and their antifungal activity or induce systemic resistance in plants. All concentrations of C. procera extracts suppressed growth of the …