Issue AddressedSubstance use and mental illness remain critical issues for young Australians, however, engagement with evidence‐based health resources is challenging among this age group. This study aimed to develop engaging, useful digital health resources, underpinned by neuroscience principles, to build awareness of the harms of electronic cigarettes (e‐cigarettes) and concurrent alcohol and antidepressant use.MethodsA mixed‐methods approach was adopted to co‐design two evidence‐based videos resources. The resources were co‐designed with the Matilda Centre's Youth Advisory Board Centre's Youth Advisory Board through a series focus groups and individual feedback reviews. Young people residing in New South Wales were then invited to complete a survey to evaluate the usefulness, relatability and impact on perceived harms associated with each substance pre‐ and post‐viewing resources.ResultsA total of 100 participants completed the survey (mean age = 21.5 years, SD = 2.77, 42% Female, 2% Non‐binary). The animated videos were well received, with the large majority (91% and 87% respectively) of participants rating them ‘excellent’ or ‘very good’. After viewing the videos, there was a significant increase in the perception of harm associated with e‐cigarette use, monthly (t(99) = 2.76, p = .003), weekly (t(99) = 4.82, p < .001) and daily (t(99) = 4.92, p < .001), and consuming alcohol whilst taking antidepressants both weekly (t(100) = 2.93, p = .004) and daily (t(100) = 3.13, p = .002).ConclusionsThis study describes a successful co‐design process demonstrating how meaningful involvement of young people, alongside traditional research methods, can produce substance use prevention resources that are useful, engaging and increase knowledge of harms among young people.So What?To achieve meaningful public health impact researchers, experts and digital creators can work together to co‐create substance use educational materials that are engaging, well‐liked, while imparting important health knowledge.