<p>The human–dog (<i>Homo sapiens–Canis familiaris</i>) relationship is humanity’s longest interspecies partnership, yet studies integrating its biological and semiotic mechanisms remain limited. This paper examines the dyad through a biosemiotic lens, synthesising evidence from evolutionary theory, ethology, physiology, and human–animal interaction. We propose that the human-dog dyad can be understood as a biologically and semiotically integrated system grounded in sign interpretation and umwelt overlap. We review bidirectional neuroendocrine, behavioural, and interpretive feedback pathways and introduce the term hominin–canine axis for this interspecific regulatory network. We also hypothesize plausible routes for co-regulation of immune function and the gut microbiome. We suggest that, in some contexts, certain dyads may exhibit superorganism-like features. By positioning the human–dog dyad as both a biological and interpretive system, this novel framework bridges biosemiotics, evolutionary theory, ethology, and human–animal interaction, offering testable hypotheses for future research and a unifying model for heterospecific integration.</p>