Chronic periodontitis is associated with coronary heart disease (CHD), including Acute Coronary Syndrome (ACS), which causes inflammation. CRP, IL-6, leukocytes, neutrophils, and lymphocytes are inflammatory mediators. This study aimed to evaluate CRP, IL6, leukocytes, and NLR effect on chronic periodontitis in ACS patients. A total of 60 ACS patients who underwent coronary angiography were used in this study. Coronary artery assessment was measured based on QCA coronary angiography. Periodontal status measured were Oral Hygiene Index (OHI-S), Bleeding on Probing (BOP), and Periodontal Index (PI). The normal-mild limit values of chronic periodontitis were periodontal depth (PD) <4mm, while the moderate-severe of chronic periodontitis was PD ≥ 4 mm. Correlation of CRP, IL-6, leukocytes, and NLR to chronic periodontitis was determined by the Spearman correlation test, followed by path analysis using smartPLS software version 3.0. Additionally, the Goodness of Fit analysis and logistic regression was also conducted. Moderate-severe and normal-mild of chronic periodontitis were found in 45 patients (75%) and 15 patients (25%), respectively. OHI-S, BOP, and PI in moderate-severe chronic periodontitis were significantly higher than in the normal-mild chronic periodontitis group (p<0.05). A comparison of CRP, IL-6, leukocytes and NLR showed no significant value (p>0.05) in both groups. There was no significant positive relationship between CRP, IL-6, leukocytes, and NLR with chronic periodontitis. No direct effect of CRP, IL-6, leukocytes and NLR on chronic periodontitis was found, but female sex and smoking directly affected chronic periodontitis (p<0.05). Female and smoking patients had a higher risk of developing more severe chronic periodontitis with a female OR value of 6.916 (95% CI: 0.470 – 101.798), while the OR smoking was 10.759(95% CI: 1.064 – 108.762). ACS patients were dominated by moderate to severe chronic periodontitis and had worse OHI-S, BOP, and PI. There were no significant effects of CRP, IL-6, leukocytes, and NLR on chronic periodontitis. Our findings revealed a significant direct effect and a high risk of female sex and smoking against chronic periodontitis on ACS patients.