Recent studies have suggested that periodontal disease and alterations in the oral microbiome may be associated with cognitive decline and Alzheimer’s disease (AD) development. Here, we report a case-control study of oral microbiota diversity in AD patients compared to healthy seniors from Central Asia. We have characterized the bacterial taxonomic composition of the oral microbiome from AD patients (n = 64) compared to the healthy group (n = 71) using 16S ribosomal RNA sequencing. According to our results, the oral microbiome of AD has a higher microbial diversity, with an increase in Firmicutes and a decrease in Bacteroidetes in the AD group. LEfSe analysis showed specific differences at the genus level in both study groups. A region-based analysis of the oral microbiome compartment in AD was also performed, and specific differences were identified, along with the absence of differences in bacterial richness and on the functional side. Noteworthy findings demonstrated the decrease in periodontitis-associated bacteria in the AD group. Distinct differences were revealed in the distribution of metabolic pathways between the two study groups. Our study confirms that the oral microbiome is altered in AD. However, a comprehensive picture of the complete composition of the oral microbiome in patients with AD requires further investigation.