You can parametrize such sets and then consider the differentiability with respect to the parameters. The differentiability property will be invariant with respect to diffeomorphisms: if two parametrizations are related by a diffeomorphism (that is, by a differentiable bijection whose inverse is also differentiable), then a function differentiable with respect to one of the two parametrizations will be differentiable with respect to the other parametrization. In general, a parametrization can be any bijection. Some parametrizations may be more useful/natural than others -- e.g., parametrizations that are homeomorphisms with respect to the natural topologies would usually be better than parametrizations that are not homeomorphisms.
E.g., you can parametrize the set $S:=\{x\in\mathbb R^3\colon x_1+x_2+x_3=1,x_i>0\ \forall i\}$ by the parametrization
$$S_1\ni(s,t)\mapsto\phi(s,t):=(s,t,1-s-t)\in S$$
or, e.g., the parametrization
$$S_2\ni(s,t)\mapsto\psi(s,t):=(1-s-t,s,t)\in S,$$
where $S_1:=S_2:=\{(s,t)\in\mathbb R^2\colon s>0,t>0,s+t<1\}$. These two parametrizations are equivalent, in the sense that they are related by a diffeomorphism -- here, specifically, by the diffeomorphism
$$S_2\ni(s,t)\mapsto g(s,t):=(1-s-t,s)\in S_1$$
in the sense that $\psi=\phi\circ g$ and hence $\phi=\psi\circ g^{-1}$.
$\big($In the above example, the domains $S_1$ and $S_2$ of the two different parametrizations $\phi$ and $\psi$ of the same set $S$ were the same.
In general, though, the domains of different parametrizations of the same set may be different. Even in the above example, another parametrization of $S$ is
$$S_3\ni(s,t)\mapsto\rho(s,t):=(s,t-s,1-t)\in S,$$
where $S_3:=\{(s,t)\in\mathbb R^2\colon0<s<t<1\}\ne S_1$. The parametrization $\rho$ is then equivalent to the parametrizations $\phi$ and $\psi$.$\big)$
A function $f\colon S\to\mathbb R$ may then be called differentiable if the function $f\circ\phi\colon S_1\to\mathbb R$ is differentiable or, equivalently, if the function $f\circ\theta$ is differentiable, where $\theta$ is any parametrization of $S$ equivalent to $\phi$. Then, by the chain rule, we also have
$$(f\circ\psi)'=(f\circ\phi\circ g)'=(f\circ\phi)'\circ g';$$
here, at each point of $S_2$, $g'$ is a linear operator from $\mathbb R^2$ to $\mathbb R^2$, and $(f\circ\phi)'$ is a linear operator from $\mathbb R^2$ to $\mathbb R$ (that is, a linear functional).
For instance, the function $S\ni x\mapsto f(x):=x_1^2+x_2x_3$ will be differentiable, because the function $S_1\ni(s,t)\mapsto (f\circ\phi)((s,t))=s^2+t(1-s-t)$ is differentiable or, equivalently, because the function $S_2\ni(s,t)\mapsto (f\circ\psi)((s,t))=(1-s-t)^2+st[=(f\circ\phi\circ g)((s,t))]$ is differentiable.
For further reading, see e.g. differentiation on manifolds.