The Safety of the Mercedes-Benz S-Class are as follow:
| Variants | 2018 Mercedes-Benz S-Class S 450 L AMG Line |
| Euro NCAP Rating | 0 |
| ASEAN NCAP Rating | 0 |
| Airbags | 10 |
| Driver/Front Passenger Seat Airbags | Y/Y |
| Front/Rear Side Airbags | Y/Y |
| Front/Rear Curtain Airbags | Y/Y |
| Knee Airbags | |
| Rear Airbags | Y |
| Airbag Disable Function | Y |
| Seatbelt Reminder | All Seats |
| Autonomous Emergency Braking | Y |
| Lane-keeping Alert | Y |
| Blind Spot Info System | Y |
| Collision Warning | Y |
| ABS/EBD | Y |
| Electronic Stability Control(ESC) | Y |
| Child Safety Lock | Manual for rear doors |
| ISOFIX | Y |
| Security Alarm | Y |
| Immobilizer | Y |
