The underlying reason comes from understanding that particles are field quanta, so properties of a particle are related to (derive from) the fields they are oscillations of. In Newtonian mechanics, a negative mass would be an oddity, in a field theory it would be cataclysmic. Negative mass means negative kinetic energy, which in field theoretic terms means the underlying field would violate the null energy condition. There isn't any a priori reason a field couldn't violate the null energy condition, but if it did, this field would be unstable - it could continuously decay to states of lower energy by particle-antiparticle pair creation. This would either continue indefinitely or until a new lowest energy vacuum state is arrived at, with some sort of condensate of this field for which its oscillations are no longer negative-mass. In our universe, the vacuum appears to be stable, and the fact that we do not observe particles of negative mass is a reflection of this fact.
Another way to think about this: if you bang on something, you generate phonons. These phonons have positive energy, and so positive mass E=mc^2.Over time, this energy dissipates, the phonons decay away, and the system settles back down to its ground state. If you "banged on" a system whose quantum oscillations have negative mass, it would dissipate energy by generating more of these oscillations, and this would continue until the system becomes saturated with these particles or explodes itself.
It is not definitively known if our vacuum is completely stable. In fact there's theoretical reasons to think it may not be. So this is not to say such a thing doesn't or can't exist, just that the these two observational facts are linked - our vacuum is stable insofar as we know, and insofar as we know there are no negative mass particles bouncing about. (There are even models of dark energy that are not observationally ruled out that violate the null energy condition and could involve negative mass particles - again if this is true it would imply some instability of our vacuum).