Background and Objectives: There has been an increasing interest in the use of non-pharmacological approaches for the multidimensional treatment of chronic pain. The aim of this systematic review was to assess the effectiveness of mindfulness-based therapies and Guided Imagery (GI) interventions in managing chronic non-cancer pain and related outcomes. Materials and Methods: Searching three electronic databases (Web of Science, PubMed, and Scopus) and following the PRISMA guidelines, a systematic review was performed on Randomized Controlled Trials (RCTs) and pilot RCTs investigating mindfulness or GI interventions in adult patients with chronic non-cancer pain. The Cochrane Risk of Bias Tool was utilized to assess the quality of the evidence, with outcomes encompassing pain intensity, opioid consumption, and non-sensorial dimensions of pain. Results: Twenty-six trials met the inclusion criteria, with most of them exhibiting a moderate to high risk of bias. A wide diversity of chronic pain types were under analysis. Amongst the mindfulness interventions, and besides the classical programs, Mindfulness-Oriented Recovery Enhancement (MORE) emerges as an approach that improves interoception. Six trials demonstrated that mindfulness techniques resulted in a significant reduction in pain intensity, and three trials also reported significant outcomes with GI. Evidence supports a significant improvement in non-sensory dimensions of pain in ten trials using mindfulness and in two trials involving GI. Significant effects on opioid consumption were reported in four mindfulness-based trials, whereas one study involving GI found a small effect with that variable. Conclusions: This study supports the evidence of benefits of both mindfulness techniques and GI interventions in the management of chronic non-cancer pain. Regarding the various mindfulness interventions, a specific emphasis on the positive results of MORE should be highlighted. Future studies should focus on specific pain types, explore different durations of the mindfulness and GI interventions, and evaluate emotion-related outcomes.