This study assessed the impact of the Chronic Disease Self-Management Program (CDSMP) on different domains of health literacy using a pre-post study design. Participants aged over 16 years and with one or more self-reported chronic diseases were recruited for the CDSMP in western Sydney (a highly diverse area of New South Wales, Australia) between October 2014 and September 2018. Health literacy was assessed pre- and immediately post-intervention using the Health Literacy Questionnaire (HLQ), with differences in mean scores for each HLQ domain analysed using paired sample t-tests. A total of 486 participants were recruited into the CDSMP. Of those, 316 (65.0%) completed both pre- and post-intervention surveys and were included in the analysis. The median age of the participants was 68 years, the majority were female (62.5%), and most were born in a country other than Australia (80.6%). There were statistically significant (p < 0.001) improvements across all nine domains of the HLQ. This is the first study evaluating the potential impact of the CDSMP on improving different domains of health literacy amongst a diverse sample of participants with chronic diseases using a multi-dimensional instrument. The absence of a control population in this study warrants caution when interpreting the results.