The present study proposed updated and standardized classification and nomenclature of eutherian adiponectin genes implicated in regulation of systemic metabolism and inflammation and activation of classical complement pathway. The revisions of comprehensive adiponectin gene data sets used eutherian comparative genomic analysis protocol and public reference genomic sequence assemblies. Among 438 potential coding sequences, the tests of reliability of eutherian public genomic sequences annotated most comprehensive curated third-party data gene data set of eutherian adiponectin genes that included 211 complete coding sequences. There were 18 major gene clusters of eutherian adiponectin genes described, one of which included evidence of differential gene expansions. For example, the present analysis initially described human ADIF2 and ADIR genes. Finally, the tests of protein molecular evolution using relative synonymous codon usage statistics confirmed protein primary structure similarities between eutherian adiponectins and tumor necrosis factor ligands.