Sensory abnormalities, including altered olfaction, represent potential diagnostic criteria for autism spectrum disorder (ASD). Atypical GABAergic neurons have been extensively described in ASD animal models. Olfactory brain regions contain a large subpopulation of GABAergic interneurons that express somatostatin (Sst). However, the role of Sst-expressing interneurons in olfactory processing in ASD remains unclear. In this study we evaluated the mRNA expression of GABAergic synaptic components in the olfactory bulb and frontal cortex, the number of GABAergic postsynaptic puncta in primary olfactory neurons in vitro and in the piriform cortex in vivo, the morphology of Sst interneurons isolated from the olfactory bulb, and the density of Sst cells in the piriform cortex of Shank3-deficient (-/-) mice, which exhibit autism-like behavior. Gene expression analysis revealed significantly lower mRNA levels of the GABAA receptor ɣ1 subunit (Gabrg1) in the olfactory bulb and collybistin (Arhgef9) in the frontal cortex of Shank3-/- mice compared to WT mice. A similar trend was observed for Sst mRNA expression in the frontal cortex of Shank3-/- mice. SHANK3 deficiency significantly reduced GABAergic puncta in primary olfactory neurons, as well as in the piriform cortex. The morphological characteristics of neurites were significantly different in Sst interneurons isolated from Shank3-/- mice. Additionally, an altered number of Sst cells was discovered in the piriform cortex of Shank3-/- mice. These findings suggest that GABAergic synaptic abnormalities and Sst interneuron morphological changes in olfactory brain regions are implicated in ASD-like conditions. Supported by APVV-21-0189 and VEGA 2/0057/23.