Previous studies have suggested that gut microbiota plays a critical role in colorectal cancer (CRC). Although preliminary comparisons of the oral and gut microbiota between CRC and healthy control (HC) patients have been made, the association between microbiome abundance and host clinical factors has not been fully illustrated, especially oral health conditions. Matching samples of unstimulated saliva, cancer tissues or biopsies and stools were collected from 30 CRC and 30 HC patients from Shanghai Jiao Tong University affiliated Renji Hospital for 16S rRNA sequencing analysis. The diversity in salivary and mucosal microbiome, but not stool microbiome of CRC group, was significantly different from that of HC, as demonstrated by the Principal Component Analysis. Logistic regression analysis revealed that older age and higher oral hygiene index (OHI) were independent risk factors for CRC, with odds ratios and 95% confidence intervals of 1.159 (1.045‐1.284) and 4.398 (1.328‐14.567), respectively. Salivary Firmicutes to Bacteroides ratio in CRC was significantly higher than that in the HC group (P < .001), while the mucosal ratio was slightly decreased in CRC (P < .05). Salivary Rothia and Streptococcus levels were positively correlated with OHI, while Alloprevotella, Fusobacterium, Peptostreptoccus and Prevotella genera levels were negatively associated with OHI. NetShift analysis revealed that salivary Peptococcus, Centipeda and mucosal Subdoligranulum genus might act as key drivers during the process of carcinogenesis. In conclusion, the current study provides insights into the potential influence of host clinical factors on oral and gut microbiome composition and can be a guide for future studies. What's new? The oral microbiota has been reported to play a critical role in the pathogenesis of colorectal cancer and may provide diagnostic biomarkers. However, oral health status, which might impact the composition of the oral microbiome, is also important to consider. Here, by integrating 16S rRNA sequencing, face‐to‐face questionnaires, and bioinformatics analysis, the authors systematically compared the oral and gut microbiota of colorectal cancer patients with healthy controls. In addition, they analysed the associations between several hosts' clinical parameters and the 50 most abundant oral and gut genera, providing potential diagnostic and therapeutic targets for colorectal cancer.