Purpose: Mandibular two-implant overdentures opposing conventional complete maxillary dentures have been proposed as the standard for complete denture service. Monitoring marginal bone loss around implants is regarded as the most important criterion in determining the success of implants. The aim of this systematic literature review was to critically evaluate the literature on short- and long-term marginal bone loss associated with mandibular two-implant overdentures using different loading protocols. Materials and Methods: The MEDLINE, EMBASE, and PubMed (using medical subject headings) databases were searched using the restriction of articles in English only. Other articles were identified from the reference lists of the articles found, as well as from early online articles. Reviewed studies were those on two oral implants supporting mandibular overdentures with different loading protocols. Marginal bone loss was evaluated as well as the validity of using marginal bone loss measurements for determining the success of implants. Results: Twenty-five studies met the review criteria. Clinical studies involving conventional loading showed longterm results; however, early and immediate loading protocols were only in the short term. High success or survival rates of two implants supporting mandibular overdentures were reported, regardless of the loading protocol. A lack of standardization was revealed in the radiographic methods used for measuring marginal bone loss and the success criteria on which results were based. Long-term outcomes of the effect of different loading protocols on marginal bone loss were not found. Due to the wide methodologic variation among the included studies, it was difficult to compare data between studies or to determine long-term marginal bone loss patterns with this treatment. For conventional two-stage and one-stage loading protocols, the range of marginal bone loss seen in the first year was 0.2 to 0.7 mm and 0.0 to 2.0 mm, respectively. For early loading protocols, the range was 0.0 to 0.2 mm; immediate loading protocols saw a marginal bone loss of around 0.7 mm in the first year. Conclusions: Short-term findings indicate that so far, there is no detrimental effect on marginal bone levels with early and immediate loading protocols. However, to recommend these protocols in the long-term for two implants supporting mandibular overdentures may be premature.