Background <p>Infant colic, defined by excessive crying following the ‘Rule of Threes’, remains an enigmatic and challenging phenomenon with an unclear etiology. While organic causes are rare, differences in sensory processing are increasingly recognized as playing a significant role. This study aimed to investigate the sensory processing profiles of infants diagnosed with colic compared to non-colicky peers.</p> Methods <p>A cross-sectional comparative design was used. We assessed the sensory processing patterns of 7–12 month old infants with colic (<i>n</i> = 40) and age-matched non-colicky controls (<i>n</i> = 40) using the Infant/Toddler Sensory Profile–2 (ITSP-2). The ITSP-2 evaluates four sensory quadrants: Low Registration, Sensation Seeking, Sensory Sensitivity, and Sensation Avoiding.</p> Results <p>Colicky infants exhibited significantly higher reactivity and processing difficulties across <i>all</i> assessed sensory domains including tactile, vestibular, oral, and behavioral areas compared to non-colicky controls. Notably, colicky infants showed pronounced challenges in tactile and vestibular processing, suggesting early neuro-regulatory dysfunction. A complex, paradoxical profile was observed, characterized by the simultaneous presence of high Sensory Sensitivity and high Low Registration.</p> Conclusion <p>Our findings suggest that developmental difficulties in sensory input modulation may be associated with colic etiology. These results highlight that developing intervention strategies that focus on sensory processing difficulties, beyond traditional gastrointestinal or behavioral approaches to improve self-regulation and alleviate colic symptoms, may also be important for managing these problems.</p>