Background: Serum thymus and activation-regulated chemokine (TARC) and periostin are reliable biomarkers in eosinophilic asthma. Objective: This study was carried out to determine the use of periostin and TARC as biomarkers in asthma and to compare the superiority of one over the other, especially in asthma with an eosinophilic phenotype. Methods: The study was conducted with 87 patients with asthma and 42 healthy control subjects. Patients with asthma were also divided into eosinophilic and non-eosinophilic phenotypes. A pulmonary function test was performed in all the participants, and serum and induced sputum TARC, periostin concentrations, eosinophils, and total immunoglobulin E values were examined. Results: TARC and periostin levels were significantly higher in the asthma group than in the control group (p < 0.001). The serum TARC level in the eosinophilic group was significantly higher than in the non-eosinophilic and control groups (p < 0.001). The induced sputum TARC level was significantly higher in the non-eosinophilic group than in the control group (p < 0.001). The TARC and periostin levels of the patients were evaluated by using receiver operator characteristic analysis. The cutoff value for TARC was determined to be 1415.39 ng/L; likewise, the cutoff value for periostin was 107.60 ng/L. The present study detected that serum levels of TARC correlated to serum levels of periostin (r = 0.54; p = 0.032). Furthermore, when evaluating correlations between serum and sputum levels, there was a correlation detected between TARC and periostin in serum, whereas this correlation was stronger in sputum: r = 0.66, p = 0.020; and r = 0.62, p = 0.028, respectively. Conclusion: Serum and sputum TARC and periostin may contribute for monitoring the improvement of patients, particularly those with asthma. Furthermore, TARC was a more reliable biomarker than periostin for patients with eosinophilic asthma. OT CO