Analgesic medications in dentistry are indicated for the relief of acute pain, postoperative pain, chronic pain as well as controlling adjunctive intraoperative pain. The use of nonsteroidal anti-inflammatory drugs (NSAIDs) has shown an effective reduction of postendodontic pain by action on the cyclooxygenase pathway. Another medication which is used recently is corticosteroid which enables the reduction of pain. They are hormones secreted from the adrenal gland and have strong anti-inflammatory actions. This review aims to compare the analgesic efficacy of NSAIDs and corticosteroids when administered through oral route for reducing postendodontic pain. The secondary objective was to assess the anesthetic effect of the nerve block when an oral premedication of NSAIDs or corticosteroids was administered. The databases of PubMed, ScienceDirect, LILACS, and Cochrane were searched for related topics from 1983 to April 2020. Bibliographies of clinical studies were identified in the electronic search. Clinical studies with postendodontic pain reduction using NSAIDs and corticosteroids were selected. Clinical studies that met all inclusion criteria were reviewed. Data extraction was performed independently by two reviewers. All individuals who administered single dose analgesic (NSAID or corticosteroid) before initiating root canal treatment were taken into inclusion criteria. All the relevant data were extracted from the selected studies were reviewed by two independent reviewers using a standardized data collection form, and in case of disagreement, a third reviewer was enquired to achieve a consensus. Risk of bias of the selected studies was done using Cochrane Risk of Bias Tool (version 1). Mean pain score levels at various time intervals showed an increased analgesic success rate for corticosteroids ( 32-1) in comparison to NSAIDs ( 32-21.4). Anesthetic effect of the nerve block administered was seen to be better when an oral premedication of corticosteroids (38.2%-80.8%) was given in comparison to NSAID (25.5%-73.1%). From the present study, it can be concluded that oral administration of corticosteroids provides a better analgesic efficacy when compared to NSAIDs as an oral premedication for postoperative pain reduction. It can also be concluded that corticosteroids when used as an oral premedication provide a better anesthetic effect of the nerve block administered when compared to NSAIDs given as an oral premedication. These findings could help the clinician determine which pretreatment analgesic would have a better effect in reduction of pain posttreatment as well as increasing the anesthetic efficacy of administered block. Systematic Review Registration Number: CRD42021235394.