D-lactate encephalopathy is a rare but serious complication in patients with short bowel syndrome (SBS), characterized by neurological symptoms resulting from the accumulation of D-lactic acid. This chapter explores the pathophysiology of D-lactic acidosis, emphasizing the role of altered gut microbiota, impaired metabolism due to enzymatic inhibition, and disrupted acid–base balance. The reduced absorptive capacity in SBS increases carbohydrate fermentation in the colon, promoting overproduction of D-lactate by specific bacterial strains. Diagnostic challenges arise due to limited access to D-lactate assays and nonspecific clinical manifestations such as ataxia, confusion, and altered mental status. This chapter outlines diagnostic markers, including metabolic acidosis with a high anion gap, and highlights key therapeutic approaches: rehydration, electrolyte correction, modulation of gut flora, and, in severe cases, hemodialysis or surgical intervention. Awareness and timely management are essential to prevent neurological complications and improve patient outcomes.