Mild Cognitive Impairment (MCI) is a heterogenous neuropsychological syndrome with high risk of progression to various neurodegenerative diseases especially Alzheimer’s disease (AD). Although the late stage of MCI is associated with neuro-modulatory kynurenine pathway (KP) dysregulation, the role of KP-induced neuroinflammation in MCI is still unclear. In addition, the lack of definite therapeutic treatment in MCI brings the concept of using mind-body therapies as alternative treatments to modulate the disease process. This study aimed to investigate the effect of short-term mindfulness meditation practice on the KP metabolites, enzymes and its modifying factors amongst the MCI population. Participants attending the memory clinics at Hospital Tuanku Ja’afar, Malaysia with Monteral Cognitive Assessment test score of 18-25 were randomized into meditation group (n=17, mean age 66.7±6.6 years) undertaking mindfulness practice (30 minutes daily following the audio guided instruction for 21 days) and non-meditation group (n=19, mean age 69.2±8.7 years) which served as control. Mindfulness meditation practice significantly increased serum concentrations of KP inducer, interferon-gamma (IFN-γ), (p<0.05), significantly decreased that of tryptophan (TRP) (p<0.05), and kynurenine (KYN) (p<0.05). Although not significant, higher serum concentrations of neuroprotectant picolinic acid (PIC), and lower concentrations of neurotoxic metabolites, 3-hydroxykynurenine (3-HK) and quinolinic acid (QUIN) were observed after practice. No significant changes were noted for other studied KP modifying factors; perceived negative emotional status assessed by depression, anxiety, stress scores (DASS-21), serum concentrations of cortisol, and brain-derived neurotrophic factor (BDNF). In addition, no changes in cardiovascular parameters (systolic-, diastolic- and mean arterial blood pressures and heart rate) were noted. As for the control group, serum concentrations of cortisol (p<0.01) and IFN-γ (p<0.001) were higher while TRP (p<0.05) were lower at 21 days. However, no significant changes in perceived emotional states, cardiovascular reactivity and KP metabolites were noted with a trend of increase in QUIN concentrations after 21 days. The observed decreasing trends of neurotoxic metabolites, 3-HK and QUIN, and the increasing trend of neuroprotective metabolite (PIC) may potentially ameliorate the neuroinflammatory process of MCI among the meditation group. The preliminary findings in this study highlight the need for longitudinal studies with larger sample sizes of longer interventional periods.