Keselamatan dari Mercedes-Benz GLE-Class adalah sebagai berikut:
| Varian | Mercedes-Benz GLE-Class 400 Coupe 4MATIC AMG Line | Mercedes-Benz GLE-Class 450 4MATIC AMG Line | Mercedes-Benz GLE-Class AMG 43 4MATIC Coupe |
| Peringkat Euro NCAP | |||
| Peringkat ASEAN NCAP | |||
| Jumlah airbag | |||
| Airbag kursi penumpang / utama | |||
| Airbag sisi depan / belakang | |||
| Airbag lutut | |||
| Pengingat sabuk pengaman | |||
| Active emergency braking system | |||
| Tire Pressure Monitoring System (TPMS) | Y | Y | Y |
| Lane Departure Warning System (LDWS) | |||
| Lane Keeping Assist System (LKAS) | |||
| Collision avoidance system(CAS) | |||
| Anti-lock Braking System (ABS) | |||
| Electronic Brake-force Distribution (EBD) | Y | Y | Y |
| Sistem kontrol traksi | |||
| Vehicle Stability Control (VSC) | |||
| Child safety lock | Y | Y | Y |
| ISOFIX | |||
| Security alert | |||
| Immobilizer | Y | Y | Y |
