Smart biodegradable tough interpenetrating polymer networks (IPNs) of bio-based polyurethane containing a silicone moiety and polystyrene at three different compositions were synthesized for the first time by using simultaneous polymerization technique. The structures of the synthesized IPNs were interpreted by FTIR, NMR, and XRD analyses, while morphology was provided from a SEM study. The synthesized IPNs exhibited outstanding elongation at break (up to 1608%) along with good tensile strength (up to 12.6 MPa), toughness (up to 92.34 MJ m⁻³), impact resistance (up to 26.8 kJ m⁻¹), scratch resistance (up to 6.5 kg) and durometer hardness (up to 86 Shore A). Furthermore, the synthesized IPNs exhibited good thermal stability up to 245 °C and chemical resistance. Interestingly, these IPNs showed multi-stimuli responsive self-healing (within 62 s at 450 W microwave and 6–8 min under sunlight) and shape memory (100% shape recovery within 48 s with a 450 W microwave and 7–13 min under direct sunlight) behavior. A self-cleaning attribute was also observed for the synthesized IPNs which showed a static contact angle up to 120.8° and angle of hysteresis <5°. Most interestingly, the synthesized IPNs also exhibited moderate bio-degradation under the exposure to a P. aeruginosa bacterial strain. Therefore, the synthesized smart bio-degradable tough IPNs with the above properties have great potential for different advanced multifaceted applications.