Standard equipment for the M-Class includes front airbags, sidebags in the front and windowbags. Sidebags for the rear are available as an option. The airbags provide protection adequate to each situation. For example in a head-on collision, the front airbags are deployed in two stages, depending on the severity of the impact.

If a Mercedes-Benz child seat with transponder is fitted on the front-passenger seat, the automatic child seat recognition, which is available as an option, can prevent the front-passenger front airbag from deploying. Belt tensioner, sidebag and windowbag remain active in order to protect the young seat occupant.

An additional roll-over sensor in the airbag control unit can trigger all of the belt tensioners and both windowbags in certain roll-over situations.

In the event of a severe side-on collision, the windowbags and sidebags offer additional protection. The windowbag unfolds like an inflatable curtain between the A and C-pillars, offering extra protection for passengers both in the front and rear.

The further developed crash-responsive NECK-PRO head restraint system, designed to reduce the risk of whiplash injuries, is available for the front seats. NECK-PRO is fully integrated into the front head restraints and supports the head earlier in the event of a rear-end collision. If the sensors register a crash, they release a pre-tensioned spring that pushes the head restraints forwards and upwards. After deployment, the head restraints can be pushed back to their original position by hand. Another novelty is the seat belt warner for the front seats.

Even before a crash occurs, the M-Class can prepare for the impact: the standard PRE-SAFE® system triggers preventive measures in the decisive moments before an accident occurs. If the sensors recognise an emergency braking situation or heavy oversteer or understeer, PRE-SAFE® causes the front seat belts to be pulled taut by means of electric motors as a precaution and the front passenger seat is moved into a better position to cope with the impact (this function is only available in conjunction with the memory package). In driving situations with a high level of transversal dynamics indicating the vehicle is in imminent danger of a side-on collision or of overturning, the side windows and the sunroof (if fitted) are automatically closed. When the danger has passed, the tension in the seat belts is released. All the other components involved can then be returned to their original positions.