The disinfection efficacy of standalone chlorine, UV and their combined approach (hybrid) was investigated for the coliform removal in BioKube 1 and 2 treated effluents collected from different environmental settings of clinical and domestic wastes. Chlorine and UV disinfection were applied to BioKube treated wastewater with doses from 0 to 4 mg L−1 and 0–166 mJ cm−2 respectively. Combined disinfection strategies were designed to reduce the dose of chlorine and UV and to exploit the synergistic effect of them. The culturable coliforms were enumerated in treated wastewater sample (control), immediately after (reduction), and 24 h post disinfections (regrowth) using culture media plating and colilert-18 media. Both the BioKube systems (1 and 2) were effective in achieving the strict norms of physicochemical parameters, but not following the coliform counts of treated effluent for reuse in irrigation. A hybrid strategy of chlorine followed by UV was found to be the most effective among various standalone and combination approaches for the removal of coliforms (>4 log ER or <1000 CFU/100 mL) from both the treated effluents. However, coliform present in treated effluent of BioKube 1 were resisting (regrowth) against all kind of applied disinfectants except chlorine followed by UV dose at or more than 0.5 mg L−1 + 41 mJ cm−2. Limited reports are available on hybrid disinfection approaches with decentralized packaged sewage treatment units and this study would help to adopt as an effective tertiary treatment strategy for reuse of treated sewage for irrigation while ensuring public health safety.