Background The primary objective of root canal therapy is to eliminate bacteria from the root canal system of teeth. However, standard chemo-mechanical disinfection has been found unable to remove bacteria within the root canals. Clinicians tempted to use additional disinfection techniques to achieve adequate level of disinfection. There is no such systematic review that could comprehensively compare the efficiency of all currently used disinfection techniques. This systematic review aims to compare the antimicrobial effectiveness of various adjunctive disinfection techniques with standards chemo-mechanical disinfection technique(needle syringe irrigation) used during root canal therapy in patients with pulp necrosis and apical periodontitis.Methods A well-defined structured clinical question in the form of PICO (Patients/Problem, Intervention, Comparison, Outcome) is designed. The unit of analysis in this review is a tooth. Teeth with apical periodontitis is a problem (P). Interventions (I) are supplemental disinfection techniques that include photodynamic therapy, passive ultrasonic irrigation, and negative pressure techniques. Comparison (C) will be standard chemo-mechanical disinfection technique. Outcome (O) is the effectiveness of antimicrobial activity in the form of detection of bacteria and colony-forming units (CFU). Keywords, MeSH terms, and synonyms will be searched through previous literature, books, and Medline database. We will perform a comprehensive search strategy using electronic databases MEDLINE (Ovid), EMBASE (Ovid), and Cochrane library. Hand searching of top endodontic journals and reference lists of selected studies will be carried out. Selection of studies will be made under predefined inclusion and exclusion criteria. Data extraction of selected studies will be done with two reviewers using a structured data collection form. At the same time, the risk of bias using the Cochrane risk of bias assessment tools will be carried out. A qualitative and quantitative data synthesis will be done. The data will be presented in the form of tables of summary of findings.Discussion All potential clinical, methodological, and patient's related factors responsible for heterogeneity will be explored and discussed. We will also compare the results of our systematic review with existing literature. Strength and limitations of the systematic review will be discussed.Systematic Review registration Our protocol is registered with the International Prospective Register of Systematic Reviews (PROSPERO-CRD#42019099141).