Background: Many middle-aged and older adults have more than one chronic health condition. It is therefore important to explore the effectiveness of interventions for multiple chronic conditions. Tai Chi is widely used in China and other countries, and many studies have examined the effect of Tai Chi on anxiety and depression. However, there are no systematic reviews of the effect of Tai Chi on anxiety and depression in various chronic conditions. This systematic review and meta-analysis aimed to evaluate the effects of Tai Chi on anxiety and depression symptoms in four chronic conditions: cancer, stroke, heart failure (HF), and chronic obstructive pulmonary disease (COPD). Methods: We searched Chinese and English databases (Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), Wanfang Database, and Sinomed) from inception to October 2020. Review Manager version 5.2 and Stata version 12.0 were used to perform a systematic review. The quality of the included studies was evaluated using the Cochrane risk of bias tool. The study was registered with the PROSPERO database (number CRD42020209594). Results: Of the 596 studies identified, we included 25 randomized controlled trials involving 1819 participants. Combined analysis of the four diseases showed statistically significant differences between the Tai Chi and control groups for anxiety symptoms (SMD -0.99, 95%CI: -1.5, -0.47; P < 0.01) and depressive symptoms (SMD 0.70, 95%CI: -1.01, -0.39; P < 0.01). Subgroup analyses showed statistically significant differences between the Tai Chi and control groups for depressive symptoms in stroke (SMD -0.43, 95%CI: -0.67, -0.18; P < 0.01) and HF (SMD -0.57, 95%CI: -0.8, -0.33; P < 0.01). However, no statistically significant differences were found for depressive symptoms in COPD or cancer. There were statistically significant differences between the Tai Chi and control groups for anxiety symptoms in stroke (SMD -0.60, 95%CI: -0.88, -0.32; P < 0.01) and cancer (SMD -0.69, 95%CI: -1.22, -0.17; P < 0.01), but not in COPD or HF. Subgroup, sensitivity, meta regression, and publication bias analyses showed high heterogeneity correlated with a single study and study quality. Sensitivity analysis showed that most meta-analysis results had good stability, but those for anxiety symptoms in COPD were unstable; therefore, careful interpretation is required. Conclusion: Tai Chi has a positive effect on anxiety and depression, especially for patients with cancer, stroke, and HF. However, given the weak evidence, this approach is not a substitute for psychiatric treatment.