Damping-off diseases caused huge losses in crop production in numerous countries. Pythium aphanidermatum represents a major cause of these diseases. In the present investigation, two endophytic fungi Talaromyces omanensis and Aspergillus fumigatus isolated from a desert plant, Rhazya stricta, were investigated for their efficiency in suppressing P. aphanidermatum and its stimulated damping-off diseases in cucumber and radish. The results proved the ability of both endophytes to inhibit P. aphanidermatum growth in both solid and liquid forms, inhibit its oospore production, induce abnormal patterns in its hyphae and suppress its induced damping-off diseases. Moreover, T. omanensis produced an inhibition zone area against P. aphanidermatum and enhanced the fresh weight of cucumber and length, fresh weight and dry weight of radish. Further, A. fumigatus caused cellular leakage in P. aphanidermatum mycelium. The previous results were interpreted through the secretion of β-1,3-glucanase, cellulase and siderophore by both endophytic fungi.