Due to the COVID-19 pandemic, in December 2020, the Italian government established a second home confinement during the Christmas holidays. These restrictions offered the opportunity to utilize a well-defined model for observing the consequences of lifestyle changes of healthy individuals. This study aimed at estimating in healthy subjects from Southern Italy the physical activity (PA), the presence and the severity of gastrointestinal (GI) symptoms, and the association between the possible worsening of GI health status and the PA levels. An adapted version of the International PA Questionnaire-short form (IPAQ-SF) and the Gastrointestinal Symptom Rating Scale (GSRS) were proposed through Google’s online survey platform in three different periods via WhatsAppTM to 499 healthy subjects (62% females) from Apulia (25%), Calabria (37%), and Campania (38%). Our results showed statistically significant changes during the home confinement: reduced energy expenditure (EE) among overweight subjects (−239.82, 95%CI −405.74; −73.89) or those who had high GSRS total score (−1079.54, 95%CI −2027.43; −131.66). An increase in GSRS total score was observed in overweight subjects, reaching statistical significance in those from Campania. Our study supports the importance of PA to reduce health risks, including those related to the possible onset of GI tract diseases.