Temporomandibular joint disorders (TMDs) are prevalent musculoskeletal conditions involving pain and dysfunction of jaw mobility and function, which have proven difficult to treat satisfactorily. The present study aimed to assess the effectiveness of a liquid platelet-rich fibrin (i-PRF) infusion during arthrocentesis versus other options using coadjuvant materials to reduce TMD symptoms. A literature search was conducted using PubMed, EMBASE, Web of Science, Scopus, and ClinicalTrials.gov for RCTs published before January 2024, comparing i-PRF to any other TMD treatment. This systematic review was registered on PROSPERO (CRD42023495364). The searches generated several recent RCTs that compared i-PRF injection combined with arthrocentesis (AC) to AC-only or AC with platelet-rich plasma (PRP). The outcomes analyzed included measures of pain (visual analog scale, VAS), maximum mouth opening, joint sounds, and MRI-verified changes in joint structure. Across the RCTs, the addition of i-PRF injection to AC resulted in significant improvements in pain relief, joint function, mouth opening, and structural changes compared to AC-only or with PRP over follow-up periods ranging from 6 to 12 months. Current clinical evidence favors using i-PRF as an adjunct to AC rather than AC-only or AC with PRP for the treatment of TMDs. The improvements in subjective and objective outcome measures are clinically meaningful. Still, additional high-quality RCTs with larger sample sizes and longer follow-ups are required to strengthen the evidence base and better define the role of i-PRF in TMD management guidelines.