Balantioides coli is a protozoan that infects different hosts species, including humans, with zoonotic transmission. The parasite, which lives in the large intestine and in other organs, can lead to serious infections that may culminate in death. Information about human balantidiasis is generally still very scanty. In view of the above, the purpose of this study was to analyze the epidemiological, clinical and laboratory characteristics of human balantidiasis based on a systematic review and meta-analysis. The scientific articles were retrieved from various databases and were subjected to descriptive analyses, chi-squared tests, and summarized on a forest plot and the heterogeneity index (I2). A total of 103 articles were eligible and included in this review. Out of these 103 articles, 75 were clinical case reports and 28 were epidemiological studies, indicating a frequency of 997 (3.98%) people potentially infected with B. coli. The publication dates of the analyzed articles ranged from 1910 to 2020, but the majority (68.9%) were published between 1998 and 2020. A considerable number of these articles were published in South America and Asia, mostly in Brazil and India, respectively. However, in Africa, Ethiopia, was observed the higher number of infected people (47.5%). A significant association (p < 0.05) was identified between proximity to pigs and positivity for B. coli, since more than 16% infected people were in proximity with pigs and/or their excreta. Infection by the protozoan was classified mainly as intestinal, and the predominant symptom was dysentery. Extraintestinal infections were found in 27 individuals, with colonization of the genitourinary tract frequently highlighted. Direct examination (17.2%), followed by an association of direct examination and sedimentation (45.7%), were the most commonly performed parasitological techniques, and the most frequently diagnosed form was trophozoites, corresponding to 22.5% of cases. The most common treatment for parasitized individuals (11.8%) was an association of tetracycline drugs with nitroimidazole derivatives. The articles retrieved, mainly epidemiological ones, used in meta-analysis showed high heterogeneity (I2> 50%, p < 0.05), impairing the retrieval and comparison of results. Some articles were found to provide incomplete information, making it difficult to retrieve and analyze variables. However, this review enabled us to compile and restate factors that appear to be associated with cases of human balantidiasis.