Elevated soluble cluster of differentiation 163 (sCD163) concentrations, a marker of macrophage activation, are associated with obesity. Weight reduction decreases circulating CD163 levels, and changes in sCD163 levels are associated with improved metabolic dysfunction. Currently, the relationship between sCD163 and diet remains unclear. This study investigated dietary patterns associated with sCD163 concentrations and its predictive effect on metabolic syndrome (MetS). Data on anthropometrics, blood biochemistry, and a food frequency questionnaire were collected from 166 Taiwanese adults. sCD163 levels independently predicted MetS (odds ratio (OR): 5.35; 95% confidence interval (CI): 2.13~13.44, p < 0.001), non-alcoholic fatty liver disease (OR: 2.19; 95% CI: 1.03~4.64, p < 0.001), and central obesity (OR: 3.90; 95% CI: 1.78~8.55, p < 0.001), after adjusting for age and sex. An adjusted linear regression analysis revealed strong correlations between levels of sCD163 and aspartate transaminase (AST) (β = 0.250 (0.023~0.477), p < 0.05) and red blood cell aggregation (β = 0.332 (0.035~0.628), p < 0.05). sCD163-associated dietary pattern scores (high frequencies of consuming noodles and desserts, and eating at home, and a low intake frequency of steamed/boiled/raw food, white/light-green-colored vegetables, orange/red/purple-colored vegetables, dairy products, seafood, dark-green leafy vegetables, and soy products) were positively correlated with MetS, liver injury biomarkers, and sCD163 levels (all p for trend < 0.05). Individuals with the highest dietary pattern scores (tertile 3) had a 2.37-fold [OR: 2.37; 95% CI: 1.04~5.37, p < 0.05] higher risk of MetS compared to those with the lowest scores (tertile 1). Overall, the study findings suggest the importance of a healthy dietary pattern in preventing elevated sCD163 levels and diet-related chronic disease such as MetS.