© 2020, The Author(s). Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorders (HSD) are heritable connective tissue disorders associated with pain, activity limitations and participation restrictions. A key feature is reported to be reduced stiffness and increased extensibility and elasticity of connective tissues. Yet diagnosis relies on assessment of joint range of motion, which may be influenced by other factors, and semi-quantitative assessment of forearm skin extensibility. Theobjective of this systematic review was to determine if quantitative measures of tissue mechanics can discriminate between hEDS/HSD and healthy tissues. Literature was identified via online databases (AMED, CINAHL+, EMBASE, MEDLINE and SportDiscus) and snowballing. Studies were included if participants had a confirmed diagnosis of hEDS/HSD (or equivalent diagnosis) using internationally recognised criteria, a healthy control group was used as a comparator, and objective measures of tissue stiffness, extensibility or elasticity of muscle, tendon, connective tissue or skin were reported. Included studies were critically appraised, followed by group discussion, consensus and narrative synthesis. Two hundred three potentially relevant studies were identified. Application of the inclusion criteria resulted in four studies being included. A range of quantitative approaches to studying tissue mechanics were used, including diagnostic ultrasound. Overall, three of the four studies found that at least one measure of tissue mechanics distinguished between people with hEDS/HSD and healthy controls. The studies were generally conducted and reported to high standards. Quantitative measures of tissue mechanics have the potential to contribute towards more objective diagnosis of hEDS/HSD. Further validation, particularly within diagnostic scenarios, is required.