Background: Runs of homozygosity (ROHs) and heterozygosity (ROHets) serve for the identification of genomic regions as candidates of selection, local adaptation, and population history. Methods: The present study aimed to comprehensively explore the ROH and ROHet patterns and hotspots in Greek native dairy goats, Eghoria and Skopelos, genotyped with the Illumina Goat SNP50 BeadChip. SNP and functional enrichment analyses were conducted to further characterize hotspots and the candidate genes located within these genomic regions. Genetic relationships between and within breeds and inbreeding coefficients were also evaluated. Results: Clear genetic differentiation and diversified management practices were depicted between the two native populations. The ROH and ROHet average genome coverage for Skopelos (65.35 and 35 Mb) and Eghoria (47.64 and 43 Mb) indicated differences in mainland and insular goats, with Skopelos showing more long ROH fragments, reflecting its geographic isolation and small population size. An ROH hotspot (CHR12: 43.59–44.61 Mb) detected in the Skopelos population has been also reported across European goats and co-localizes with a selection signal detected in the Egyptian Barki goats and sheep adapted to hot–arid conditions. A novel ROH hotspot (CHR18: 60.12–61.81 Mb), shared among the Greek breeds, harbors candidate genes enriched in biosynthesis, metabolism, and immune response. Two well-conserved ROHet islands were detected in Greek goats on chromosomes 1 and 18, with genes participating in development and embryogenesis. The Eghoria population showed the highest number of ROHet islands, potentially reflecting its adaptability to diverse environments. Conclusions: These findings offer new insights into the environmental adaptation and artificial selection in Greek goats and could be utilized in future breeding strategies for sustainable goat farming.