Objective: This review focuses on the in vitro degradation of eggshell-based hydroxyapatite for analyzing the weight loss of hydroxyapatite when applied in the human body. Cytotoxicity tests were used to observe cell growth and morphological effects. A systematic review and meta-analysis were conducted to observe the weight loss and viable cells of hydroxyapatite when used for implants. Method: Based on the Population, Intervention, Comparison, and Outcome (PICO) strategy, the articles used for literature review were published in English on SCOPUS, PubMed, and Google Scholar from 1 January 2012 to 22 May 2021. Data regarding existing experiments in the literature articles the in vitro degradation and cytotoxicity testing of eggshell-based hydroxyapatite determined the biocompatibility of the materials. A meta-analysis was conducted to calculate the mean difference between the solutions and soaking times used for degradation and the stem cells used for cytotoxicity. Results: From 231 relevant studies, 71 were chosen for full-text analysis, out of which 33 articles met the inclusion criteria for degradation and cytotoxicity analysis. A manual search of the field of study resulted in three additional articles. Thus, 36 articles were included in this systematic review. Significance: The aim of this study was to highlight the importance of the biocompatibility of eggshell-based hydroxyapatite. The weight loss and viability cells of eggshell-based hydroxyapatite showed optimum results for viable cells requirements above 70%, and there is a weight loss of eggshell-based hydroxyapatite for a material implant. The meta-analysis indicated significant differences in the weight loss of eggshell-based hydroxyapatite materials with different soaking times and solutions used. The various kinds of stem cells for incubation of cultured cells in contact with a device, either directly or through diffusions with various kinds of stem cells from animals and humans, yielded viability cells above 70%.