Background: Alexithymia, a predictor in chronic illnesses, like cardiovascular and bipolar disorder (CD–BD), could be improved with a virtual reality (VR) cognitive remediation program. This secondary analysis of a previous randomized controlled trial (RCT) evaluates alexithymia improvement and its factors in an experimental group versus a control group, exploring extensions to individuals with comorbid non-psychiatric chronic conditions. Methods: A feasibility cross-over RCT (ClinicalTrials.gov NCT05070065) enrolled individuals aged 18–75 with mood disorders (BD, DSM-IV), excluding those with relapses, epilepsy, or severe eye conditions due to potential risks with VR. Alexithymia levels were measured using the Toronto Alexithymia Scale with 20 items (TAS-20). Results: The study included 39 individuals in the experimental group and 25 in the control group, with no significant age or sex differences observed. Significantly improved alexithymia scores were noted in the experimental group compared to controls (F = 111.9; p < 0.0001) and in subgroups with chronic non-psychiatric comorbidities (F = 4.293, p = 0.048). Scores were particularly improved for difficulty in identifying feelings (F = 92.42; p < 0.00001), communicating feelings (F = 61.34; p < 0.00001), and externally oriented thinking (F = 173.12; p < 0.00001). Conclusions: The findings highlight alexithymia enhancement in BD, even with comorbid non-psychiatric chronic diseases. Given its impact on BD progression and related conditions, like CD, developing and evaluating VR-based tools in this context is suggested by these findings.