Abstract Introduction Two biomarkers that are gaining attention for their roles in the progression of both periodontal and cardiovascular diseases are vitronectin and fetuin‐A. This study evaluated vitronectin and fetuin‐A expression in saliva samples of periodontitis (P) patients with and without coronary artery disease (CAD) after scaling and root planing (SRP). Methods Sixty patients were divided into three groups: PH + SH (periodontally and systemically healthy), P (stage II/III grade B periodontitis), and P + CAD (periodontitis with CAD). Demographic, periodontal, and cardiac parameters were recorded. Unstimulated saliva samples were collected at baseline (day 0) and after SRP. On day 90, periodontal parameters and vitronectin/fetuin‐A expression were reassessed. Results P + CAD patients had higher age, weight, BMI, and lower income ( p < .001, .025, .002, < .001, respectively), along with elevated plaque index, bleeding on probing, probing pocket depth, and reduced clinical attachment levels ( p < .001). Vitronectin was elevated, while fetuin‐A was lower in P + CAD, but both improved post‐SRP ( p < .001). Conclusions Enhanced vitronectin and fetuin‐A levels post‐SRP indicate their potential as biomarkers and therapeutic targets for both periodontal and CAD.