Context: The ineffective disinfection potential of conventional intracanal medicaments to eliminate enteropathogens from root canal systems leads to their persistence contributing to endodontic treatment failures. Hence, the use of appropriate intracanal medicament becomes the essential phase to accomplishing comprehensive decontamination of the root canal system. When applied topically as an intracanal medicament, antibiotics eradicate residual microorganisms from tortuous endodontic spaces, minimizing the risk of systemic toxicity. Aims and objectives: To evaluate the prevalence of various bacterial species associated with signs of irreversible pulpitis and pulp necrosis with/without abscess in primary teeth root canals and their susceptibility against three antimicrobial agents. Materials and methods: The pulp tissue and organic debris were retrieved from deciduous teeth (n = 50) from children between the age of 3–10 years and cultured. The bacterial identification and antibacterial profiling of isolated bacteria were done against clindamycin, metronidazole, and doxycycline through minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assay. The MIC and MBC of each antibiotic were expressed as mean ± standard deviation (SD), range, and standard error (SE of the mean). The intergroup comparisons were done by the Kruskal–Wallis test, while intragroup pair-wise comparisons were done using the Wilcoxon signed-rank test. The confidence level will be set at 95%. Results: Aerobic bacteria were found in 54%, microaerophilic bacteria in 76%, facultative anaerobes in 26%, and obligatory anaerobes were isolated from 30% of teeth. The intragroup and intergroup comparisons of test agent MIC revealed a nonsignificant difference (p > 0.05). The intragroup MBC comparisons of all the test agents revealed statistically nonsignificant (p > 0.05), while intergroup comparisons demonstrated nonsignificant (p > 0.05) to highly significant difference (p < 0.001). Conclusion: Clindamycin demonstrated promising antibacterial activity against most of the isolated bacteria, while against metronidazole and doxycycline, most of the bacteria were moderate to highly resistant. Clinical significance: Determining the antibacterial agents' efficacy along with modifications can help to target maximum pathogenic microbes and reduce catastrophic endodontic therapy failures.