The Referral Back Program (Program Rujuk Balik/PRB) aims to improve the effectiveness of healthcare services for patients with chronic diseases, such as hypertension and diabetes mellitus (DM). The success of this program is strongly influenced by patients’ ability to understand health information and their capacity to independently manage medication therapy at home. This study aims to analyze the relationship between health literacy and independence in therapy management among Referral Back Program (PRB) patients at Kimia Farma HB Jassin Pharmacy, Gorontalo City. This study employed a descriptive quantitative method with a cross-sectional approach. The sample consisted of 75 PRB patients selected using purposive sampling, comprising 57 patients with hypertension and 47 patients with DM, including patients with comorbidities. The instruments included the HLS-EU-Q16, HSMBQ, and IDN-DSMI 35 questionnaires. Data were analyzed using univariate and bivariate analyses with the Gamma correlation test. The Gamma statistical test showed no significant relationship between health literacy and independence in therapy management among patients with hypertension (p-value = 0.401; p > 0.05). In contrast, a significant positive relationship of moderate strength was found between health literacy and independence in therapy management among patients with diabetes mellitus (p-value = 0.026; p < 0.05). Therefore, health literacy is significantly associated with independence in therapy management among patients with diabetes mellitus, but is not significantly associated with therapy management independence among patients with hypertension at Kimia Farma HB Jassin Pharmacy.