Timely and accurate medication intake remains one of the most persistent challenges in patient care, with non-adherence often leading to severe health complications and increased healthcare costs. This research proposes a novel IoT-enabled Smart Medicine Box that combines embedded systems, cloud connectivity, and real-time user interaction to create a comprehensive medication management solution. Unlike conventional pillboxes, the system is designed to dynamically schedule reminders based on daily routines, odd/even days, or specific weekdays, thereby offering flexibility for diverse treatment plans. The ESP32 microcontroller manages core system operations such as highlighting the correct medicine compartment through LEDs, generating audio reminders via a buzzer, and displaying information on the LCD screen. The system designed also supports caregivers by delivering real-time notifications, maintaining dosage records, and tracking medication stock levels. In this, a dual confirmation mechanism is provided that relies on both patient acknowledgment and automatic stock verification to validate successful medication intake. This facilitates to minimize missed or double doses. Moreover, it enhances transparency in patient–caretaker communication. The experimental results demonstrate the system’s reliability in real-time operation that shows potential to be a scalable, low-cost solution for home-based healthcare.