Background <p><i>Colpodella</i> species are classified within the domain Eukaryota, specifically under the order Colpodellida, family Colpodellaceae, and genus <i>Colpodella</i>, which are close relative of the phylum Apicomplexa. These organisms are unicellular, predatory flagellates. In recent years, their frequent detection in animal tissues, vector insect samples, and particularly in human has garnered significant attention as an emerging zoonotic threat. This review is to scope the biological characteristics and epidemiological features of <i>Colpodella</i> species.</p> Methods <p>The PubMed, Web of Science, and China National Knowledge Infrastructure databases were searched to identify studies in English or Chinese published before 4 February 2025. We searched for <i>Colpodella</i>-related nucleotide sequences released in the GenBank before 31 December, 2024. The literature and sequences were selected based on predefined inclusion criteria. We extracted the characteristics of <i>Colpodella</i> spp. from included articles and performed a phylogenetic analysis based on the included sequences.</p> Results <p>Thirty-seven records and 83 sequences were included in the study, respectively. <i>Colpodella</i> spp. currently comprise only two formally named species, alongside at least 11 species&#xa0;uncultured or unnamed in GenBank. Their life cycle includes trophozoite and cyst stages, with nutrient acquisition mediated by myzocytosis. These organisms display structural and protein similarities in their apical complexes to apicomplexan protozoa, yet with distinct differences. They are currently found in a wide range of hosts, including humans, livestock, pets, wildlife and vectors, across multiple continents, including Europe, Asia, Africa, and the Americas. Phylogenetic analyses reveal that <i>Colpodella</i> spp. exhibit significant genetic diversity and can be divided into seven clades, each characterized by distinct host ranges and regional distributions, and three clades posed pathogenic potential and significant risk of human infection.</p> Conclusions <p>This study systematically elucidates the broad host/vector range, genetic diversity and public health implications of <i>Colpodella</i> species based on comprehensive integrated genomic and epidemiological analyses. We recommend establishing active surveillance networks using clade-specific molecular markers for hosts and vectors in high-risk regions, incorporating <i>Colpodella</i> screening into routine diagnostics for fever cases of unknown origin with anaemia, prioritizing studies on isolation and cultivation, biological characteristics, and clade-specific in vitro invasion assays to elucidate the pathogenic mechanisms.</p> Graphical Abstract <p></p>