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Simple Summary: Fungal root rot and wilt diseases are among the most urgent obstacles to roselle production as they attack seedlings and mature plants, causing significant yield losses. Outbreaks of such diseases can be prevented with chemical fungicides. Unfortunately, the excessive use of fungicides can pollute the environment and cause harmful effects in humans and animals. Therefore, a number of biotic and abiotic inducers were selected for the induction of systemic resistance (ISR) in roselle. The used inducers have shown a good ability to inhibit the growth of pathogenic fungi in vitro, and strongly reduce disease development in vivo. With the view that plants can defend themselves through a variety of chemical mechanisms, we estimated the phytochemicals and the activities of defensive enzymes. In conclusion, ISR has become a good target for suppressing roselle root rot and wilt, and promoting crop growth without environmental risks. The possibility of inducing systemic resistance in roselle against root rot and wilt diseases was investigated using biotic and abiotic inducers. The biotic inducers included three biocontrol agents (i.e., Bacillus subtilis, Gliocladium catenulatum, and Trichoderma asperellum) and two biofertilizers (i.e., microbein and mycorrhizeen), while the abiotic inducers included three chemical materials (i.e., ascorbic acid, potassium silicate, and salicylic acid). In addition, preliminary in vitro studies were conducted to evaluate the inhibitory activity of the tested inducers on the growth of pathogenic fungi. The results show that G. catenulatum was the most efficient biocontrol agent. It reduced the linear growth of Fusarium solani, F. oxysporum, and Macrophomina phaseolina by 76.1, 73.4, and 73.2%, respectively, followed by B. subtilis by 71.4, 69, and 68.3%, respectively. Similarly, potassium silicate was the most effective chemical inducer followed by salicylic acid, each at 2000 ppm. They reduced the linear growth of F. solani by 62.3 and 55.7%; M. phaseolina by 60.7 and 53.1%; and F. oxysporum by 60.3 and 53%, respectively. In the greenhouse, all inducers applied as a seed treatment and/or foliar spray strongly limited the development of root rot and wilt diseases. In this regard, G. catenulatum, at 1 × 109 CFU mL−1, achieved the highest values of disease control, followed by B. subtilis; while T. asperellum, at 1 × 105 CFU mL−1, recorded the lowest values. In addition, the plants treated with potassium silicate followed by salicylic acid, each at 4 g/L, recorded the highest disease control compared to ascorbic acid at 1 g/L, which had the lowest values. The mixture of mycorrhizeen + microbein (at 10 g/kg seeds) was the most effective compared to either of them alone. All treatments, applied alone or in combination in the field, significantly reduced the incidence of diseases. The most effective treatments were a mixture of G. catenulatum (Gc) + Bacillus subtilis (Bs) + Trichoderma asperellum (Ta); a mixture of ascorbic acid (AA) + potassium silicate (PS) + and salicylic (SA); G. catenulatum; potassium silicate; and a mixture of mycorrhizeen + microbein. Rhizolix T had the highest disease-reducing efficacy. In response to the treatments, significant improvements in growth and yield, changes in biochemicals, and increased activities of defense enzymes were achieved. This research points to the activity of some biotic and abiotic inducers that can play a vital role in managing the root rot and wilt of roselle through the induction of systemic plant resistance. [ABSTRACT FROM AUTHOR]