Various theoretical models of Health Literacy (HL) discuss its importance for behaviour change, supporting long-term health and disease prevention. During the 21st century Physical Activity (PA), Exercise and Sedentariness (SD) have received an increased priority over other health indices for quality of life purposes due to their central importance over metabolic conditions and their comorbidities. This review aims to conceptualise the main issues and challenges of Physical Inactivity (PI) and SD through the new proposals of Design Thinking (DT) which is considered one of the most promising pathways in health promotion. DT is prioritising empathy for service users, brings together collaborative multidisciplinary teams and provides the opportunity to assess various solutions via iterative practices. This chapter: A. provides a review over the efficacy of health promotion strategies during the current era and the urgency of behaviour change in PA and SD for various population segments. B. Explains how HL links self-care practices to PA and SD habits. And C. Presents DT as a new layout for supporting the exploration and feasibility of more active lifestyles for overall health and quality of life.