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This study investigates the potential of native biocontrol agents (BCAs) as controls againstGanoderma lucidumcausing root rot mortality in Indian mesquite. The disease is prevalent in sandy soils where trees grow under rainfed conditions. In addition, a beetle namelyAcanthophorus serraticornisdamages the roots, resulting in increasing vulnerability of the host thereby allowing easy of the pathogen. In dual culture tests, Ganoderma infected cowpea root bit experiment and compatibility with insecticides revealed that the three BCAs (Trichoderma longibrachiatum,T. harzianum,andAspergillus nidulans) significantly inhibitedG. lucidummycelial growth. The highest mycelial growth inhibition (47.6%) was recorded after 96 h followed by 39.8% and 29.3% at 72 and 48 h, respectively, byT. longibrachium. Cell free filtrates ofT. longibrachiatum,T. harzianum,andA. nidulanswere superior in inhibiting mycelium growth. A low concentration (3 ml) ofT. longibrachiatumwas more effective in inhibiting mycelium growth compared to other BCAs. BothProsopis julifloracompost and onion residue compost amendments as food substrates favored the growth of these BCAs, which ultimately reduced the viability ofGanoderma-colonized root bits of cowpea. Studies on compatibility between insecticides and BCAs suggests thatT. longibrachiatum,harzianum and A. nidulanscan be combined with phorate or chloropyriphos (both organophosphates) at variable concentrations if amended together for partially infected trees, or as a prophylactic measure in healthy trees. These studies demonstrate that there is considerable opportunity for using native BCAs againstG. lucidumin managing root rot disease.