In this study, several bio-agents, including Trichoderma album, T. hamatum, T. harzianum and T. viride; prepared as suspensions at a concentration of 30×10⁶ conidia/ ml, in addition to bio-fungicides, such as Plant Guard (T. harzianum, 30×10⁶) and Bio-zeid (T. album, 10×10⁶), demonstrated significant in vitro and in vivo antagonistic efficacies against certain soil-borne fungal pathogens, which cause root rot diseases of cantaloupe plants during the growing seasons of 2019/ 2020 and 2020/ 2021. In the in vitro assays, T. harzianum caused a significant reduction of the pathogens' radial mycelial growth, including Rhizoctona solani, Phytophthora spp., Sclerotium rolfsii and Fusarium oxysporum by 79.69 %, followed by T. viride (76.26 %), and T. album (70.82 %), respectively. On the other hand, T. hamatum expressed the least antagonistic potential and decreased the pathogens' growth by 66.01 % only. In vivo assay results showed that applying inocula of 1 l/100 l water/ Feddan of the bio-control agents against the cantaloupe root rot pathogens significantly reduced the disease incidence, which recorded the highest reduction percentages of 79.66 % and 77.07 % by T. harzianum, during the two growing seasons of 2019/ 2020 and 2020/ 2021, respectively. Moreover, these applied bio-agents promoted the growth parameters and chemical components of the cantaloupe plants significantly, including percentage of the total soluble solids, total phenol content, protein, nitrogen, ascorbic acid, and total sugars, thus increasing the crop yield. The current work aimed to reduce the use of toxic chemical fungicides during the agriculture process, to produce safe food of high quality and quantity, and to find the most suitable bio-agent that has the ability to protect and control the cantaloupe plants against the soil-borne fungal diseases under the impact of climate change.