Haritalodes derogata (Fabricius) (Lepidoptera: Crambidae), commonly known as the cotton leaf roller, is an important polyphagous pest that causes damage to various agricultural and forest plants, especially those of the Malvaceae family, but also to crops such as cotton, cashew, bamboo, oats, and jute. While microbial control agents are known for their efficacy and environmental friendliness, there are few studies demonstrating their effect on H. derogata. The aim of this study was to evaluate the bioefficacy of microbial agents from different pathogen groups against this pest. To this end, we investigated the insecticidal potential of fifteen indigenous microbial isolates from our entomopathogen collection. These included five Bacillus thuringiensis strains (Bn1, MnD, Mm2, Xd3, Lyd8), five entomopathogenic fungi (Metarhizium flavoviride As2, M. anisopliae KTU-51 and Beauveria bassiana Pa4, Pa5, Hp5), and five baculoviruses (HycuGV-Hc1, LdMNPV-T2, AcMNPV, DapuNPV-T1, SeMNPV-U), applied at concentrations of 1.8 × 109 cfu/mL, 1 × 107 conidia/mL, and 1 × 107 PIB/mL, respectively, against H. derogata larvae under laboratory conditions. Among these, B. thuringiensis subsp. kurstaki Bn1, B. bassiana Pa4, Hyphantria cunea granulovirus (HycuGV-Hc1), and Spodoptera exigua nucleopolyhedrovirus (SeMNPV-U) showed strong insecticidal activity and were selected for virulence assays, each achieving 100% mortality in third instar larvae. The median lethal concentrations (LC50) were determined to be 7.1 × 104 cfu/mL, 3.3 × 103 conidia/mL, 1.2 × 103 PIB/mL, and 1 × 103 PIB/mL, respectively. These results indicate that indigenous microbial agents are a promising environmentally friendly alternative to chemical pesticides in the control of H. derogata.